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1. Improving feature interactions at Pinterest under industry constraints

Author

Malreddy, Siddarth, Lawhon, Matthew, Nookala, Usha Amrutha, Mantha, Aditya, and Badani, Dhruvil Deven

Subjects
Computer Science - Information Retrieval
Abstract

Adopting advances in recommendation systems is often challenging in industrial settings due to unique constraints. This paper aims to highlight these constraints through the lens of feature interactions. Feature interactions are critical for accurately predicting user behavior in recommendation systems and online advertising. Despite numerous novel techniques showing superior performance on benchmark datasets like Criteo, their direct application in industrial settings is hindered by constraints such as model latency, GPU memory limitations and model reproducibility. In this paper, we share our learnings from improving feature interactions in Pinterest's Homefeed ranking model under such constraints. We provide details about the specific challenges encountered, the strategies employed to address them, and the trade-offs made to balance performance with practical limitations. Additionally, we present a set of learning experiments that help guide the feature interaction architecture selection. We believe these insights will be useful for engineers who are interested in improving their model through better feature interaction learning.

Published
2024

2. Structural and Electrical Properties of Grafted Si/GaAsSb Heterojunction

Author

Abbasi, Haris Naeem, Lee, Seunghyun, Jung, Hyemin, Gajowski, Nathan, Lu, Yi, Wang, Linus, Kim, Donghyeok, Zhou, Jie, Gong, Jiarui, Chae, Chris, Hwang, Jinwoo, Muduli, Manisha, Nookala, Subramanya, Ma, Zhenqiang, and Krishna, Sanjay

Subjects
Physics - Applied Physics, Condensed Matter - Materials Science
Abstract

The short-wave infrared (SWIR) wavelength, especially 1.55 um, has attracted significant attention in various areas such as high-speed optical communication and LiDAR systems. Avalanche photodiodes (APDs) are a critical component as a receiver in these systems due to their internal gain which enhances the system performance. Silicon-based APDs are promising since they are CMOS compatible, but they are limited in detecting 1.55 um light detection. This study proposes a p-type Si on n-type GaAs0.51Sb0.49 (GaAsSb) lattice matched to InP substrates heterojunction formed using a grafting technique for future GaAsSb/Si APD technology. A p+Si nanomembrane is transferred onto the GaAsSb/AlInAs/InP substrate, with an ultrathin ALD-Al2O3 oxide at the interface, which behaves as both double-side passivation and quantum tunneling layers. The devices exhibit excellent surface morphology and interface quality, confirmed by atomic force microscope (AFM) and transmission electron microscope (TEM). Also, the current-voltage (I-V) of the p+Si/n-GaAsSb heterojunction shows ideal rectifying characteristics with an ideality factor of 1.15. The I-V tests across multiple devices confirm high consistency and yield. Furthermore, the X-ray photoelectron spectroscopy (XPS) measurement reveals that GaAsSb and Si are found to have type-II band alignment with a conduction band offset of 50 meV which is favorable for the high-bandwidth APD application. The demonstration of the GaAsSb/Si heterojunction highlights the potential to advance current SWIR PD technologies., Comment: 14 pages, 6 figures

Published
2024

4. Inshrinkerator: Compressing Deep Learning Training Checkpoints via Dynamic Quantization

Author

Agrawal, Amey, Reddy, Sameer, Bhattamishra, Satwik, Nookala, Venkata Prabhakara Sarath, Vashishth, Vidushi, Rong, Kexin, and Tumanov, Alexey

Subjects
Computer Science - Machine Learning
Abstract

With the increase in the scale of Deep Learning (DL) training workloads in terms of compute resources and time consumption, the likelihood of encountering in-training failures rises substantially, leading to lost work and resource wastage. Such failures are typically offset by a checkpointing mechanism, which comes at the cost of storage and network bandwidth overhead. State-of-the-art approaches involve lossy model compression mechanisms, which induce a tradeoff between the resulting model quality (accuracy) and compression ratio. Delta compression is then used to further reduce the overhead by only storing the difference between consecutive checkpoints. We make a key enabling observation that the sensitivity of model weights to compression varies during training, and different weights benefit from different quantization levels (ranging from retaining full precision to pruning). We propose (1) a non-uniform quantization scheme that leverages this variation, (2) an efficient search mechanism that dynamically finds the best quantization configurations, and (3) a quantization-aware delta compression mechanism that rearranges weights to minimize checkpoint differences, thereby maximizing compression. We instantiate these contributions in Inshrinkerator - a framework for DL workload checkpoint compression. Our experiments show that Inshrinkerator consistently achieves a better tradeoff between accuracy and compression ratios compared to prior works, enabling a compression ratio up to 39x and withstanding up to 10 restores with negligible accuracy impact for fault-tolerant training. Inshrinkerator achieves at least an order of magnitude reduction in checkpoint storage overhead for training failure recovery as well as transfer learning use cases without any loss of accuracy.

Published
2023

5. Adversarial Robustness of Prompt-based Few-Shot Learning for Natural Language Understanding

Author

Nookala, Venkata Prabhakara Sarath, Verma, Gaurav, Mukherjee, Subhabrata, and Kumar, Srijan

Subjects
Computer Science - Computation and Language, Computer Science - Machine Learning
Abstract

State-of-the-art few-shot learning (FSL) methods leverage prompt-based fine-tuning to obtain remarkable results for natural language understanding (NLU) tasks. While much of the prior FSL methods focus on improving downstream task performance, there is a limited understanding of the adversarial robustness of such methods. In this work, we conduct an extensive study of several state-of-the-art FSL methods to assess their robustness to adversarial perturbations. To better understand the impact of various factors towards robustness (or the lack of it), we evaluate prompt-based FSL methods against fully fine-tuned models for aspects such as the use of unlabeled data, multiple prompts, number of few-shot examples, model size and type. Our results on six GLUE tasks indicate that compared to fully fine-tuned models, vanilla FSL methods lead to a notable relative drop in task performance (i.e., are less robust) in the face of adversarial perturbations. However, using (i) unlabeled data for prompt-based FSL and (ii) multiple prompts flip the trend. We further demonstrate that increasing the number of few-shot examples and model size lead to increased adversarial robustness of vanilla FSL methods. Broadly, our work sheds light on the adversarial robustness evaluation of prompt-based FSL methods for NLU tasks., Comment: Accepted full paper at Findings of ACL 2023; Code available at https://github.com/claws-lab/few-shot-adversarial-robustness

Published
2023

6. ANNETTE: Accurate Neural Network Execution Time Estimation with Stacked Models

Author

Wess, Matthias, Ivanov, Matvey, Nookala, Anvesh, Unger, Christoph, Wendt, Alexander, and Jantsch, Axel

Subjects
Computer Science - Machine Learning, Computer Science - Hardware Architecture
Abstract

With new accelerator hardware for DNN, the computing power for AI applications has increased rapidly. However, as DNN algorithms become more complex and optimized for specific applications, latency requirements remain challenging, and it is critical to find the optimal points in the design space. To decouple the architectural search from the target hardware, we propose a time estimation framework that allows for modeling the inference latency of DNNs on hardware accelerators based on mapping and layer-wise estimation models. The proposed methodology extracts a set of models from micro-kernel and multi-layer benchmarks and generates a stacked model for mapping and network execution time estimation. We compare estimation accuracy and fidelity of the generated mixed models, statistical models with the roofline model, and a refined roofline model for evaluation. We test the mixed models on the ZCU102 SoC board with DNNDK and Intel Neural Compute Stick 2 on a set of 12 state-of-the-art neural networks. It shows an average estimation error of 3.47% for the DNNDK and 7.44% for the NCS2, outperforming the statistical and analytical layer models for almost all selected networks. For a randomly selected subset of 34 networks of the NASBench dataset, the mixed model reaches fidelity of 0.988 in Spearman's rank correlation coefficient metric. The code of ANNETTE is publicly available at https://github.com/embedded-machine-learning/annette.

Published
2021
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7. Hemodynamic latency is associated with reduced intelligence across the lifespan: an fMRI DCM study of aging, cerebrovascular integrity, and cognitive ability

Author

Anderson, Ariana E, Diaz-Santos, Mirella, Frei, Spencer, Dang, Bianca H, Kaur, Pashmeen, Lyden, Patrick, Buxton, Richard, Douglas, Pamela K, Bilder, Robert M, Esfandiari, Mahtash, Friston, Karl J, Nookala, Usha, and Bookheimer, Susan Y

Subjects
Aging, Acquired Cognitive Impairment, Brain Disorders, Clinical Research, Behavioral and Social Science, Dementia, Cardiovascular, Heart Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Adolescent, Adult, Aged, Aged, 80 and over, Brain, Brain Mapping, Cerebrovascular Disorders, Hemodynamics, Humans, Intelligence, Longevity, Magnetic Resonance Imaging, Middle Aged, Risk Factors, Young Adult, Hemodynamic response function, Dynamic causal modeling, Cognition, Cerebrovascular, Vascular dementia, fMRI, Medical Physiology, Cognitive Sciences, Developmental Biology, Neurology & Neurosurgery
Abstract

Changes in neurovascular coupling are associated with both Alzheimer's disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18-85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minimal cognitive demands. The hemodynamic latency (transit time) in the visual cortex was used to predict general cognitive ability (Full-Scale IQ), controlling for demographic variables (age, race, education, socioeconomic status) and cerebrovascular risk factors (hypertension, alcohol use, smoking, high cholesterol, BMI, type 2 diabetes, cardiac disorders). Increased hemodynamic latency in the visual cortex predicted reduced cognitive function (p

Published
2020

8. Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

Author

Parga, Joanna J, Lewin, Sharon, Lewis, Juanita, Montoya-Williams, Diana, Alwan, Abeer, Shaul, Brianna, Han, Carol, Bookheimer, Susan Y, Eyer, Sherry, Dapretto, Mirella, Zeltzer, Lonnie, Dunlap, Lauren, Nookala, Usha, Sun, Daniel, Dang, Bianca H, and Anderson, Ariana E

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Chronic Pain, Pain Research, Bioengineering, Neurosciences, Clinical Research, Machine Learning and Artificial Intelligence, Networking and Information Technology R&D (NITRD), Abdominal Pain, Acoustics, Colic, Crying, Female, Humans, Infant, Infant Behavior, Infant, Newborn, Machine Learning, Male, Mobile Applications, Pain Perception, Pattern Recognition, Automated, Signal Processing, Computer-Assisted, Sound Spectrography, Paediatrics and Reproductive Medicine, Public Health and Health Services, Pediatrics, Paediatrics
Abstract

BackgroundTo characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful.MethodsAssessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic.ResultsThe cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p

Published
2020

9. Gradient Nonlinear Pancharatnam-Berry Metasurfaces

Author

Tymchenko, Mykhailo, Gomez-Diaz, J. Sebastiàn, Lee, Jongwon, Nookala, Nishant, Belkin, Mikhail A., and Alù, Andrea

Subjects
Physics - Optics
Abstract

We apply the Pancharatnam-Berry phase approach to plasmonic metasurfaces loaded by highly nonlinear multi-quantum well substrates, establishing a platform to control the nonlinear wavefront at will based on giant localized nonlinear effects. We apply this approach to design flat nonlinear metasurfaces for efficient second-harmonic radiation, including beam steering, focusing, and polarization manipulation. Our findings open a new direction for nonlinear optics, in which phase matching issues are relaxed, and an unprecedented level of local wavefront control is achieved over thin devices with giant nonlinear responses.

Published
2015

10. A system to build distributed multivariate models and manage disparate data sharing policies: implementation in the scalable national network for effectiveness research

Author

Meeker, Daniella, Jiang, Xiaoqian, Matheny, Michael E, Farcas, Claudiu, D’Arcy, Michel, Pearlman, Laura, Nookala, Lavanya, Day, Michele E, Kim, Katherine K, Kim, Hyeoneui, Boxwala, Aziz, El-Kareh, Robert, Kuo, Grace M, Resnic, Frederic S, Kesselman, Carl, and Ohno-Machado, Lucila

Subjects
Distributed Computing and Systems Software, Information and Computing Sciences, Clinical Research, Biomedical Research, Comparative Effectiveness Research, Computer Communication Networks, Databases as Topic, Information Dissemination, Information Storage and Retrieval, Internet, Models, Statistical, Multivariate Analysis, Software, distributed analytics, federated research network, privacy-preserving network infrastructure, comparative effectiveness research, Engineering, Medical and Health Sciences, Medical Informatics, Biomedical and clinical sciences, Health sciences, Information and computing sciences
Abstract

BackgroundCentralized and federated models for sharing data in research networks currently exist. To build multivariate data analysis for centralized networks, transfer of patient-level data to a central computation resource is necessary. The authors implemented distributed multivariate models for federated networks in which patient-level data is kept at each site and data exchange policies are managed in a study-centric manner.ObjectiveThe objective was to implement infrastructure that supports the functionality of some existing research networks (e.g., cohort discovery, workflow management, and estimation of multivariate analytic models on centralized data) while adding additional important new features, such as algorithms for distributed iterative multivariate models, a graphical interface for multivariate model specification, synchronous and asynchronous response to network queries, investigator-initiated studies, and study-based control of staff, protocols, and data sharing policies.Materials and methodsBased on the requirements gathered from statisticians, administrators, and investigators from multiple institutions, the authors developed infrastructure and tools to support multisite comparative effectiveness studies using web services for multivariate statistical estimation in the SCANNER federated network.ResultsThe authors implemented massively parallel (map-reduce) computation methods and a new policy management system to enable each study initiated by network participants to define the ways in which data may be processed, managed, queried, and shared. The authors illustrated the use of these systems among institutions with highly different policies and operating under different state laws.Discussion and conclusionFederated research networks need not limit distributed query functionality to count queries, cohort discovery, or independently estimated analytic models. Multivariate analyses can be efficiently and securely conducted without patient-level data transport, allowing institutions with strict local data storage requirements to participate in sophisticated analyses based on federated research networks.

Published
2015

11. Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation

Author

Sims, Travis T., El Alam, Molly B., Karpinets, Tatiana V., Dorta-Estremera, Stephanie, Hegde, Venkatesh L., Nookala, Sita, Yoshida-Court, Kyoko, Wu, Xiaogang, Biegert, Greyson W. G., Delgado Medrano, Andrea Y., Solley, Travis, Ahmed-Kaddar, Mustapha, Chapman, Bhavana V., Sastry, K. Jagannadha, Mezzari, Melissa P., Petrosino, Joseph F., Lin, Lilie L., Ramondetta, Lois, Jhingran, Anuja, Schmeler, Kathleen M., Ajami, Nadim J., Wargo, Jennifer, Colbert, Lauren E., and Klopp, Ann H.

Published
2021
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12. pSCANNER: patient-centered Scalable National Network for Effectiveness Research

Author

Ohno-Machado, Lucila, Agha, Zia, Bell, Douglas S, Dahm, Lisa, Day, Michele E, Doctor, Jason N, Gabriel, Davera, Kahlon, Maninder K, Kim, Katherine K, Hogarth, Michael, Matheny, Michael E, Meeker, Daniella, Nebeker, Jonathan R, team, the pSCANNER, Resnic, Frederic, Khodyakov, Dmitry, Armstead, Lattice, Nagler, Travis, Morley, Sam, Anderson, Nicholas, Cooper, Dan, Phillips, Dan, Heber, David, Li, Zhaoping, Ong, Michael K, Patel, Ayan, Zachariah, Marianne, Burns, Jane C, Daniels, Lori B, Doan, Son, Farcas, Claudiu, Germann-Kurtz, Rita, Jiang, Xiaoqian, Kim, Hyeon-eui, Paul, Paulina, Taras, Howard, Tremoulet, Adriana, Wang, Shuang, Zhu, Wenhong, Berman, Douglas, Rizk-Jackson, Angela, D’Arcy, Mike, Kesselman, Carl, Knight, Tara, Pearlman, Laura, Heidenreich, Paul, Rifkin, Dena, Stepnowsky, Carl, Zamora, Tania, DuVall, Scott L, Frey, Lewis J, Scehnet, Jeffrey, Sauer, Brian C, Facelli, Julio C, Gouripeddi, Ram K, Denton, Jason, FitzHenry, Fern, Fly, James, Messina, Vincent, Minter, Freneka, Nookala, Lalit, Sullivan, Heidi, Speroff, Theodore, and Westerman, Dax

Subjects
Information and Computing Sciences, Health Services and Systems, Health Sciences, Health Services, Clinical Research, Good Health and Well Being, Computer Communication Networks, Confidentiality, Electronic Health Records, Humans, Information Dissemination, Outcome Assessment, Health Care, Patient-Centered Care, United States, United States Department of Veterans Affairs, pSCANNER team, clinical data research network, comparative effectiveness research, distributed analysis, patient-centered research, Engineering, Medical and Health Sciences, Medical Informatics, Biomedical and clinical sciences, Health sciences, Information and computing sciences
Abstract

This article describes the patient-centered Scalable National Network for Effectiveness Research (pSCANNER), which is part of the recently formed PCORnet, a national network composed of learning healthcare systems and patient-powered research networks funded by the Patient Centered Outcomes Research Institute (PCORI). It is designed to be a stakeholder-governed federated network that uses a distributed architecture to integrate data from three existing networks covering over 21 million patients in all 50 states: (1) VA Informatics and Computing Infrastructure (VINCI), with data from Veteran Health Administration's 151 inpatient and 909 ambulatory care and community-based outpatient clinics; (2) the University of California Research exchange (UC-ReX) network, with data from UC Davis, Irvine, Los Angeles, San Francisco, and San Diego; and (3) SCANNER, a consortium of UCSD, Tennessee VA, and three federally qualified health systems in the Los Angeles area supplemented with claims and health information exchange data, led by the University of Southern California. Initial use cases will focus on three conditions: (1) congestive heart failure; (2) Kawasaki disease; (3) obesity. Stakeholders, such as patients, clinicians, and health service researchers, will be engaged to prioritize research questions to be answered through the network. We will use a privacy-preserving distributed computation model with synchronous and asynchronous modes. The distributed system will be based on a common data model that allows the construction and evaluation of distributed multivariate models for a variety of statistical analyses.

Published
2014

15. Biopolymeric nanoencapsulation of model drug: Its development and characterisation.

Author

Kumar, Sushant, Venkata, Nookala, Madhav, Satheesh, and Pandey, Swarnima

Abstract

This research aimed to develop the phenytoin-loaded bionanosuspension by utilising the novel biopolymer from Juglans regia andreduce the long-term treatment cost of epilepsy and increase the efficiency of therapy. A novel biopolymer with remarkable inbuilt properties was isolated and used in the development of a nano capsulated dispersed system. The diverse proportions of phenytoin and biopolymer with different ratios 1:2, 1:3, 1:4, 1:5 and 1:8 were taken for the planning of details PJNC1-PJNC5. The bionanosuspension was assessed for dispersibility, pH, % entrapment efficiency, stability study and in vitro drug discharge. The formulation PJNC2 with 1:3 drug biopolymer proportion showed significant outcomes for various assessments with t50% of 16.51 h and r² estimation of 0.9884. PJNC2 showed 92.07%±2.5 drug delivery in 36h and was stable. The bionanosuspension was found to be stable and safe for the delivery of nanosized phenytoin utilising the biopolymer having a remarkable stabiliser cum retardant property. [ABSTRACT FROM AUTHOR]

Published
2024
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16. House dust mite‐induced asthma alters BBB integrity, increases amyloid beta accumulation, and alters brain cytokine levels in AppNL‐G‐F mice.

Author

Sahu, Bijayani, Nookala, Suba, Floden, Angela M, Ambhore, Nilesh, Venkatachalem, Sathish, and Combs, Colin K

Abstract

Background: Alzheimer's disease (AD) is an age‐related neurodegenerative disorder affecting nearly 50 million individuals worldwide. Besides aging, various comorbidities can increase the risk of AD, such as asthma. However, the molecular mechanism(s) underlying this asthma‐associated AD exacerbation is unknown. This study was designed to explore the effects of house dust mite‐induced asthma on AD‐related brain changes using the AppNL‐G‐F transgenic mouse model. Method: Male and female C57BL/6 wild type and AppNL‐G‐F mice (8‐9 months old) were exposed to either saline or house dust mite (dose: 833µg/kg in saline) every alternate day for 16 weeks. Mice were sacrificed at the end of the experiment and broncho‐alveolar lavage fluid (BALF), lungs, blood, and brains were collected. BALF was analyzed for immune cell markers, inflammatory mediators, and LDH activity. Lung sections were stained with Alcian blue and Masson's Trichrome to examine mucus and collagen production, respectively. The serum was analyzed for cytokine levels. Brain sections were immunostained for Aβ, GFAP, and collagen‐4. Finally, frozen hippocampi and cortices were used to perform Aβ ELISAs and cytokine arrays, respectively. Result: Dust‐mite exposure increased inflammatory cells, cytokine levels, and LDH activity in the BALF and increased the mucus and collagen production in the lungs from both sexes and genotypes, suggesting induction of a severe asthma‐like condition. This correlated with increased levels of serum cytokines in all dust‐mite‐exposed groups. In agreement with this peripheral change, hippocampi from asthma‐induced male and female AppNL‐G‐F mice demonstrated elevated Aβ plaque load and increased soluble Aβ 1‐40/42 and insoluble Aβ 1‐40 levels. Dust‐mite exposure also increased astrogliosis in both sexes of AppNL‐G‐F mice, as indicated by GFAP immunoreactivity. Additionally, dust‐mite exposure‐induced asthma elevated cortical levels of several cytokines in both sexes and genotypes. Finally, dust‐mite exposed groups also showed a disturbed BBB integrity in the hippocampus of AppNL‐G‐F mice, as indicated by decreased collagen‐4 immunoreactivity. Conclusion: Dust‐mite exposure induced a severe asthma‐like condition that exacerbated Aβ pathology, astrogliosis, cytokine changes, and disturbed BBB integrity in the brains of male and female AppNL‐G‐F mice. Defining the mechanisms of secondary effects of asthma on the brain may provide a novel therapeutic approach for both asthma and AD. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Visual estimation of blood loss versus quantitative blood loss for maternal outcomes related to obstetrical hemorrhage.

Author

Ayala, Michael, Nookala, Vikas, Fogel, Joshua, and Fatehi, Mary

Abstract

This study was undertaken to evaluate if there are differences between visual estimation of blood loss (EBL) and quantitative blood loss (QBL) for maternal outcomes related to obstetrical hemorrhage. This retrospective study compared EBL (n = 500) to QBL (n = 501) for outcomes of length of stay, readmission within 30 days of discharge, percent receiving blood transfusions, time between delivery to receiving blood transfusion, and postpartum hemoglobin level. The QBL group had a significantly lower mean length of stay than the EBL group (2.6 vs 3.2 days, P < 0.001). Multivariate linear regression analysis adjusting for relevant covariates had a similar finding of lower length of stay for QBL vs EBL (B = −0.13, SE = 0.01, P < 0.001). Readmission within 30 days, blood transfusion, time to transfusion since delivery, and postpartum hemoglobin did not significantly differ between the QBL and EBL groups. We recommend that clinicians adopt QBL over EBL as standard practice since QBL is associated with lower length of stay and does not negatively impact other clinical outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Bridging the communication gap in autistic children, one picture at a time.

Author

Meharwade, Priya, Nookala, Havisha, Kajjari, Shweta, Malavalli, Pooja, Hugar, Shivayogi M., and Uppin, Chaitanya

Abstract

One of the main domains of paediatric dentistry is providing oral health care, especially to the children with special needs, like those affected with autism spectrum disorder (ASD). Such children exhibit poor oral hygiene primarily due to their limited communication ability, lack of joint attention, oversensitivity to sensory stimuli and motor coordination deficits. In such cases, multiple studies suggest and emphasize on the importance of early use of interventional services. Children affected with ASD tend to be visual learners, and therefore, are better suited for visual interventional methods. Amongst which, picture exchange communication system (PECS), originally developed by Bondy-Frost, is gaining rapid momentum. It is suggested to help individuals to initiate requests and communicate their needs via picture cards; hence aid in acquiring functional communication and speech, improve socio-communicative impairments, and decrease the behavioural problems. This scoping review aims to raise awareness on PECS amongst the dental fraternity, by emphasizing its usage pertaining to dentistry. PECS though rated hard, has proved to be beneficial in improving oral hygiene practices among autistic children. [ABSTRACT FROM AUTHOR]

Published
2021
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21. Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

Author

P Nookala, Ted C. Ling, Rachel Mifflin, Jerry D. Slater, Gary Y. Yang, Baldev Patyal, Anh M. Ly, Roger Grove, and Jerry M. Slater

Subjects
Cancer Research, medicine.medical_specialty, medicine.medical_treatment, lcsh:RC254-282, Article, esophageal, 3d conformal radiotherapy, medicine, cancer, Esophagus, radiotherapy, proton, radiotherapy, esophageal, cancer, Lung, business.industry, Cancer, Perioperative, Esophageal cancer, Intensity-modulated radiation therapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Surgery, Radiation therapy, medicine.anatomical_structure, Oncology, Radiology, business, proton
Abstract

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

Published
2014
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22. Protons Offer Reduced Tissue Exposure for Patients Receiving Radiation Therapy for Pancreatic Cancer

Author

Jerry D. Slater, Anh M. Ly, Jerry M. Slater, Baldev Patyal, P Nookala, Roger Grove, Rachel Mifflin, Gary Y. Yang, and Ted C. Ling

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Cancer, medicine.disease, Malignancy, Spinal cord, Proton radiation therapy, Atomic and Molecular Physics, and Optics, Radiation therapy, medicine.anatomical_structure, Pancreatic cancer, medicine, Adenocarcinoma, Radiology, Nuclear Medicine and imaging, Radiology, Pancreas, business
Abstract

Purpose: Pancreatic cancer is a highly aggressive malignancy. Chemoradiation therapy (CRT) is used in many cases to improve local-regional control; however, toxicities associated with radiation can be significant given the location of the pancreas. The purpose of this study is to quantify the dosimetric changes seen when using photons or protons in patients receiving CRT for cancer of the pancreas. Patients and Methods: Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients underwent simulation with contrast-enhanced computed tomography imaging. Separate treatment plans using proton radiation therapy, intensity-modulated radiation therapy, and 3-dimensional photon radiation therapy modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the 3 modalities. The organs at risk evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statis...

Published
2014
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23. Ultrafast optical switching and power limiting in intersubband polaritonic metasurfaces

Author

Mann, Sander A., Nookala, Nishant, Johnson, Samuel C., Cotrufo, Michele, Mekawy, Ahmed, Klem, John F., Brener, Igal, Raschke, Markus B., Alù, Andrea, and Belkin, Mikhail A.

Abstract

Highly nonlinear optical materials with fast third-order nonlinear optical response are crucial for the operation of all-optical photonic devices, such as switches for signal processing and computation, power limiters, and saturable absorbers. The nonlinear response of traditional optical materials is weak, thus requiring large light intensities to induce significant changes in their properties. Here we show that optical control of the coupling rate in subwavelength patch antennas coupled to intersubband transitions in multi-quantum-well semiconductor heterostructures can provide a giant third-order nonlinear response, on the order of ${{3.4 \times 10}}^{- 13}{{{m}}^2}/{{\rm{V}}^2}$, with a response time ${\lt}{{2}}\;{\rm{ps}}$. We utilize this effect to realize intersubband polaritonic metasurfaces and demonstrate their operation as highly nonlinear saturable and reverse saturable absorbers, enabling optical power limiters and other elements for all-optical modulation and control. Our approach enables a plethora of compact, low-power, highly nonlinear devices with spectral, temporal, and structured wavefront responses tailored by design.

Published
2021

24. Passive proton therapy vs. IMRT planning study with focal boost for prostate cancer

Author

Stanley Barnes, Inhwan Yeo, David A. Bush, Reinhard W. Schulte, N Wang, Jerry D. Slater, P Nookala, Baldev Patyal, Ian Gordon, Gary Y. Yang, Ted C. Ling, and A Ghebremedhin

Subjects
Male, Imrt plan, Intraprostatic boost, medicine.medical_treatment, IMRT plan, Rectum, Prostate cancer, Prostate, medicine, Proton Therapy, Humans, Radiology, Nuclear Medicine and imaging, Radiation treatment planning, Proton therapy, business.industry, Research, Radiotherapy Planning, Computer-Assisted, Prostatic Neoplasms, Radiotherapy Dosage, medicine.disease, Proton plan, Radiation therapy, medicine.anatomical_structure, Oncology, Radiology Nuclear Medicine and imaging, Radiotherapy, Intensity-Modulated, Radiotherapy, Conformal, business, Nuclear medicine, Intensity modulation
Abstract

Background Exploiting biologic imaging, studies have been performed to boost dose to gross intraprostatic tumor volumes (GTV) while reducing dose elsewhere in the prostate. Interest in proton beams has increased due to superior normal-tissue sparing they afford. Our goal was to dosimetrically compare 3D conformal proton boost plans with intensity-modulated radiation therapy (IMRT) plans with respect to target coverage and avoiding organs at risk. Methods Treatment planning computer tomography scans of ten patients were selected. For each patient, two hypothetical but realistic GTVs each with a fixed volume were contoured in different anatomical locations of the prostate. IMRT and proton beam plans were created with a prescribed dose of 50.4 Gy to the initial planning target volume (PTV) including the PTV of the seminal vesicles (PSV), 70.2 Gy to the PTV of the prostate (PPS), and 90 Gy to the PTV of the gross tumor volumes (PGTVs). For proton plans, uncertainties of range and patient setup were accounted for; apertures were adjusted until the dose-volume coverage of PTVs matched that of the IMRT plan. For both plans, prescribed PTV doses were made identical to allow for comparing normal-tissue doses. Results Protons delivered more homogeneous but less conformal doses to PGTVs than IMRT did and comparable doses to PSV and PPS. Volumes of bladder and rectum receiving doses higher than 65 Gy were similar for both plans. However, volumes receiving less than 65 Gy were significantly reduced, i.e., protons reduced integral dose by 45.6 % and 26.5 % for rectum and bladder, respectively. This volume-sparing was also seen in femoral heads and penile bulb. Conclusions Protons delivered comparable doses to targets in dose homogeneity and conformity and spared normal tissues from intermediate-to-low doses better than IMRT did. Further improvement of dose sparing and changes in homogeneity and conformity may be achieved by reducing proton range uncertainties and from implementing intensity modulation.

Published
2015

25. Factors associated with increased mortality in hospitalized COVID-19 patients

Author

Shah, Chirag, Grando, Donna J., Rainess, Rebecca A., Ayad, Lydia, Gobran, Emad, Benson, Payam, Neblett, Meika T., and Nookala, Vinod

Abstract

The rapid spread of the coronavirus disease 2019 (COVID-19) epidemic has significantly impacted global health. So far, the evidence regarding the risk factors that predict the outcomes of COVID-19 patients is limited. In this study, we identified several risk factors that are associated with increased mortality in COVID-19 patients.

Published
2020
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26. Molecular characterisation of parvoviruses from domestic cats reveals emergence of newer variants in India.

Author

Mukhopadhyay, Hirak K., Nookala, Mangadevi, Thangamani, Nobal R. K., Sivaprakasam, Amsaveni, Antony, Prabhakar X., Thanislass, Jacob, Srinivas, Mouttou V., and Pillai, Raghavan M.

Abstract

Objectives The present study was undertaken to characterise the viral polypeptide 2 (VP2) gene of parvovirus from domestic cats in India. Methods The faecal samples from diarrhoeic/healthy domestic cats were collected from different geographical regions of India for screening by PCR assay followed by sequence analysis of the VP2 gene. Results Canine parvovirus (CPV)/feline panleukopenia virus (FPV) infections were found in 12 (11.3%) of 106 faecal samples tested. Two new CPV-2a (297Ala and Asn426) and three FPV strains were identified by VP2 gene analysis. Several unique and existing amino acid mutations were found, suggesting continuous evolution and emergence of newer variants. The phylogenetic analysis of the CPV sequences revealed that the two new CPV-2a strains from Mumbai (MC8) and Puducherry (P15) were clustered together in a single clade but had evolved independently and were ancestrally related to Chinese CPV-2a isolates. The FPV sequences (T-C-6 and T-C-1) from Thrissur, Kerala, formed a different clade (FPV clade) and were closely related to each other and had an ancestral relationship with an FPV isolate from the USA. Another FPV isolate from Goa (GC1) was positioned in the same clade but had evolved independently. Conclusions and relevance Detection of CPV in both diarrhoeic/healthy cats and the occurrence of FPV infection in a vaccinated cat provide new insights into parvovirus infections in cats in India. [ABSTRACT FROM AUTHOR]

Published
2017
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27. Synthesis, characterization and evaluation of antimicrobial efficacy and brine shrimp lethality assay of Alstonia scholarisstem bark extract mediated ZnONPs

Author

Supraja, Nookala, Prasad, T.N.V.K.V., Gandhi, Arumugam Dhanesh, Anbumani, Devipriya, Kavitha, P., and Babujanarthanam, Ranganathan

Abstract

Alstonia scholarisis one of the most important medicinal plants and herein, we present the synthesis of zinc oxide nanoparticles using the bark extract of Alstonia scholaris,and evaluation of their antimicrobial efficacy. Stable ZnO nanoparticles were formed by treating 90 mL of 1 mM zinc nitrate aqueous solution with 10 mL of 10% bark extract. The formation of Alstonia scholarisbark extract mediated zinc oxide nanoparticles was confirmed by UV–visible spectroscopic analysis and recorded the localized surface plasmon resonance (LSPR) at 430 nm. Fourier transform infrared spectroscopic (FT-IR) analysis revealed that primary and secondary amine groups in combination with the proteins present in the bark extract is responsible for the reduction and stabilization of the ZnONPs. The crystalline phase of the nanocrystals was determined by XRD analysis and morphology was studied using transmission electron microscopy (TEM). The hydrodynamic diameter (26.2 nm) and a positive zeta potential (43.0 mV) were measured using the dynamic light scattering technique. The antimicrobial activity of Alstonia scholarisZnONPs was evaluated (in-vitro) using disc diffusion method against fungi, Gram-negative and Gram-positive bacteria which were isolated from the biofilm formed in drinking water PVC pipelines. The results obtained suggested that ZnO nanoparticles exhibit a good anti-fungal activity than bactericidal effect towards all pathogens tested in in-vitrodisc diffusion method (170 ppm, 100 ppm and 50 ppm). Further, the toxicity of biosynthesized ZnONPs was tested against Alstonia scholaristo evaluate the cytotoxic effect that displayed LC50value of 95% confidence intervals.

Published
2018
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28. Low Dose Dasatinib Is Not As Active in a CML CP Cohort Enriched with Intermediate/High-Risk CML Chronic Phase: A Phase IIb Multi-Center Trial

Author

Abraham, Aby, Jain, Hasmukh, Bhattacharyya, Jina, Biswajit, Dubashi, PK, Jayachandran, Bhurani, Dinesh, Bala, Stalin Chowdary, Pramanik, Suman, Devadas, Santhosh, Kulkarni, Uday Prakash, Sengar, Manju, Ahmed, Rayaz, Mani, Thenmozhi, Das, Damodar, Karunakaran, Parathan, Gundeti, Sadashivudu, Pallasseri, Rasmi, Patkar, Nikhil, Nookala, Manjunath, Kayal, Smita, and Balasubramanian, Poonkuzhali

Published
2022
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30. Ultrathin gradient nonlinear metasurface with a giant nonlinear response

Author

Nookala, Nishant, Lee, Jongwon, Tymchenko, Mykhailo, Sebastian Gomez-Diaz, J., Demmerle, Frederic, Boehm, Gerhard, Lai, Kueifu, Shvets, Gennady, Amann, Markus-Christian, Alu, Andrea, and Belkin, Mikhail

Abstract

Gradient metasurfaces have recently been demonstrated to provide control of the phase of scattered fields over subwavelength scales, enabling a broad range of linear optical components in a flat, ultrathin, integrable platform. Additionally, the development of nonlinearmetasurfaces has disrupted conventional nonlinear optical device design by relaxing phase matching constraints, reducing size and dimensionality, and providing record values of localized nonlinear responses. However, extending the “flat optics” paradigm to the nonlinear case faces important challenges, since we are required to simultaneously achieve efficient frequency conversion and sub-diffractive phase control. Here, we experimentally demonstrate continuous phase control of the giant nonlinear second harmonic optical response from metasurfaces tied to intersubband transitions in semiconductor multi-quantum wells, establishing an exciting path toward realizing the vision of flat, nonlinear optics.

Published
2016

31. Investigation on identify the multiple issues in IoT devices using Convolutional Neural Network

Author

Thouti, Swapna, Venu, Nookala, Rinku, Dhruva R., Arora, Amit, and Rajeswaran, N.

Abstract

The Internet of Things (IoT) is an innovative technology that makes it possible for physical objects like sensors, cameras, household appliances, and other objects to interact and communicate with one another. The Internet of Things (IoT) devices may exchange critical data, which makes battery/power, connectivity, and security issues crucial. An automated system for identifying and reporting abnormalities to a central controller is a prerequisite for this. In order to distinguish between approved and legitimate IoT devices, this method should be able to. IoT devices that are malicious, non-IoT devices that are malicious, and other man-in-the-middle traffic sources must all be isolated to prevent noncompliance. For improved QoS management, this aids in the formulation of administrative rules and the regulation and enforcement of network traffic. A framework-based Convolutional Neural Network (CNN) is suggested in this research to discover the aforementioned problems in IoT devices. A system that classifies IoT devices into their respective categories and reliably identifies new entries has been developed based on CNN. The findings demonstrate that CNN is capable of classifying IoT devices into the appropriate categories with the necessary accuracy as well as identifying between IoT and non-IoT devices with better accuracy.

Published
2022
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32. On optimization efficiency of scalability and availability of cloud-based software services using scale rate limiting algorithm

Author

V N Reddy, Annapareddy, Kumar, A. Arun, Venu, Nookala, and Vijaya Kumar Reddy, R.

Abstract

Internet applications nowadays combine globally shared resources into a single software platform. It's a difficult technology issue to supply reports for the resource consumption among those World Wide Web applications. The formulation and simulation of spread levels were introduced in this report. Spread frequency operates together again to impose a worldwide speed restriction over revenue aggregated at several locations allowing for the synchronized monitoring of an internet company's activity. Assures that traffic delays mass transit streams act as passing through a unique, common limitation network. We describe two models overall and the other TCP-optimized—that permits network operators to expressly balance away transmission cost with network correctness, speed, and scaling. All these approaches could speed restrict 1000s of streams with little expense (less than 3% in the tested configuration). We show that with us TCP-centric architecture could scale to hundreds of servers whilst remaining resilient towards both outages and transmission postponement, suitable for countrywide telecom operators.

Published
2022
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33. FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation

Author

Dunlop, Elaine A, Seifan, Sara, Claessens, Tijs, Behrends, Christian, Kamps, Miriam AF, Rozycka, Ewelina, Kemp, Alain J, Nookala, Ravi K, Blenis, John, Coull, Barry J, Murray, James T, van Steensel, Maurice AM, Wilkinson, Simon, and Tee, Andrew R

Abstract

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant condition caused by mutations in the FLCNgene and characterized by benign hair follicle tumors, pneumothorax, and renal cancer. Folliculin (FLCN), the protein product of the FLCNgene, is a poorly characterized tumor suppressor protein, currently linked to multiple cellular pathways. Autophagy maintains cellular homeostasis by removing damaged organelles and macromolecules. Although the autophagy kinase ULK1 drives autophagy, the underlying mechanisms are still being unraveled and few ULK1 substrates have been identified to date. Here, we identify that loss of FLCN moderately impairs basal autophagic flux, while re-expression of FLCN rescues autophagy. We reveal that the FLCN complex is regulated by ULK1 and elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN, which are induced by ULK1 overexpression. In addition, our findings demonstrate that FLCN interacts with a second integral component of the autophagy machinery, GABA(A) receptor-associated protein (GABARAP). The FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein (FNIP)-1 or FNIP2 and further regulated by ULK1. As observed by elevation of GABARAP, sequestome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3 (MAP1LC3B) in chromophobe and clear cell tumors from a BHD patient, we found that autophagy is impaired in BHD-associated renal tumors. Consequently, this work reveals a novel facet of autophagy regulation by ULK1 and substantially contributes to our understanding of FLCN function by linking it directly to autophagy through GABARAP and ULK1.

Published
2014
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34. Annealing dependent synthesis of cyto-compatible nano-silver/calcium hydroxyapatite composite for antimicrobial activities.

Author

Gandhi, Arumugam Dhanesh, Kaviyarasu, K., Supraja, Nookala, Velmurugan, Rajendran, Suriyakala, Gunasekaran, Babujanarthanam, Ranganathan, Zang, Yang, Soontarapa, Khantong, Almaary, Khalid S., Elshikh, Mohamed S., and Chen, Tse-Wei

Abstract

Crystalline hydroxyapatite were synthesized from synthetic/human urine through precipitation which were further doped with silver nanoparticle for effective biomedical application. The aim were to improve overall biological compatibility of the synthesized bone-graft material even in oncogenesis cases. The thermal calcinated material was characterized by several techniques including UV–vis, Laser Raman, Fourier transmittance infrared spectroscopy, X-ray diffraction analysis, Transmission Eelectron microscopy and X-ray fluorescence spectroscopy. The quantitative and qualitative analysis revealed that the synthesized material was highly crystalline and nanosized with majority of silver and phosphate components. The antibacterial, anticancer and invitro cytotoxicity of the synthesized material was evaluated with Escherichia coli , Hela cells and brine shrimp assay, respectively. The brine shrimp assay revealed that the synthesized material is compatible with biological system, whereas anticancer activity showed the application of the synthesized biomaterial in cancer treatment in which antibacterial activity adds more advantage on preventing the bone-graft from microbial attack. [ABSTRACT FROM AUTHOR]

Published
2021
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35. Innate immune response to Francisella tularensisis mediated by TLR2 and caspase‐1 activation

Author

Li, Hanfen, Nookala, Suba, Bina, Xiaowen R., Bina, James E., and Re, Fabio

Abstract

Francisella tularensis, a gram‐negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensiswith the innate immune system. We have found that in human and mouse dendritic cells, F. tularensiselicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2‐deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS‐binding protein. F. tularensisappeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL‐1β secretion, a reflection of caspase‐1 activation, was induced by live but not heat‐killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL‐1β transcript. Our results identified activation of TLR2 and caspase‐1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis.

Published
2006
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36. Impairment of tetanus-specific cellular and humoral responses following tetanus vaccination in human lymphatic filariasis.

Author

Nookala, Suba, Srinivasan, Sundaram, Kaliraj, Perumal, Narayanan, Rangarajan Badri, and Nutman, Thomas B

Abstract

To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-gamma) response in the EN group, in that they increased IFN-gamma production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-gamma responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10.

Published
2004

37. A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice

Author

Khan, Arshad, Sayedahmed, Ekramy E., Singh, Vipul K., Mishra, Abhishek, Dorta-Estremera, Stephanie, Nookala, Sita, Canaday, David H., Chen, Min, Wang, Jin, Sastry, K. Jagannadha, Mittal, Suresh K., and Jagannath, Chinnaswamy

Abstract

Although the BCG vaccine offers partial protection, tuberculosis remains a leading cause of infectious disease death, killing ∼1.5 million people annually. We developed mucosal vaccines expressing the autophagy-inducing peptide C5 and mycobacterial Ag85B-p25 epitope using replication-defective human adenovirus (HAdv85C5) and bovine adenovirus (BAdv85C5) vectors. BAdv85C5-infected dendritic cells (DCs) expressed a robust transcriptome of genes regulating antigen processing compared to HAdv85C5-infected DCs. BAdv85C5-infected DCs showed enhanced galectin-3/8 and autophagy-dependent in vitroAg85B-p25 epitope presentation to CD4 T cells. BCG-vaccinated mice were intranasally boosted using HAdv85C5or BAdv85C5followed by infection using aerosolized Mycobacterium tuberculosis(Mtb). BAdv85C5protected mice against tuberculosis both as a booster after BCG vaccine (>1.4-log10reduction in Mtb lung burden) and as a single intranasal dose (>0.5-log10reduction). Protection was associated with robust CD4 and CD8 effector (TEM), central memory (TCM), and CD103+/CD69+lung-resident memory (TRM) T cell expansion, revealing BAdv85C5as a promising mucosal vaccine for tuberculosis.

Published
2021
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38. Validation of a novel causality assessment scale for adverse events in non-small cell lung carcinoma patients treated with platinum and pemetrexed doublet chemotherapy

Author

Sharma, Jyoti Bhagatram, Krishnamurthy, Manjunath Nookala, Awase, Ankita, Joshi, Amit, Patil, Vijay, Noronha, Vanita, Prabhash, Kumar, and Gota, Vikram

Abstract

Aim: Accurate causality assessment (CA) of adverse events (AEs) is important in clinical research and routine clinical practice. The Naranjo scale (NS) used for CA lacks specificity, leading to a high rate of false positive causal associations. NS is a simple scale for CA; however, its limitations have reduced its popularity in favour of other scales. We therefore attempted to improvise the algorithm by addressing specific lacunae in NS.Methods: We attempted to modify the existing NS by (a) changing the weightage given to certain responses, (b) achieving higher resolution to certain responses for delineating drug related and unrelated AEs and (c) modifying the slabs for classification of association as ‘likely’ and ‘unlikely’. The new scale, named as the Sharma-Nookala-Gota (SNG) algorithm, was evaluated in a training set of 19 AEs in a tertiary care cancer hospital in western India, and further validated in a set of 104 AEs. Consensus of four physician opinion was taken as gold standard for comparison.Results: Of the 19 AEs in the training set, 6 were described by the treating physician as ‘not related’ and 13 as related to the drug. The SNG algorithm had 100% concordance with physician opinion, whereas the NS had only 73.7% concordance. NS showed a tendency to misclassify AEs as ‘related’ when they were indeed ‘not related’. In the validation set of 104 AEs, NS and SNG algorithms misclassified 30 and 2 AEs, respectively, leading to a concordance of 70.2% and 98.1%, respectively, with physician opinion.Conclusion: Decisive modifications of the NS resulted in the SNG scale, with superior specificity while retaining sensitivity against the gold standard.Plain Language Summary SNG algorithm – A novel tool for causality assessment of adverse drug reactions Adverse events (AEs) can cause increased morbidity, hospitalisation, and even death. Hence it is essential to recognise AEs and to establish their correct causal relationship to a drug. Many causality assessment methods, scales and algorithms are available to assess the relationship between an AE and a drug. The Naranjo algorithm is most commonly employed in spite of its many drawbacks as it is simple to use. Concerns have been raised regarding the performance of the scale, and researchers have tried to answer them, but none of them could address all issues satisfactorily. We too experienced many problems while using it in our routine clinical practice and in clinical trials. For instance, the Naranjo scale is non-specific and shows a bias toward implicating the drug as the causal factor for AEs. This improper assessment has often led to drug discontinuation, thereby compromising the efficacy of treatment. Hence, we modified the existing Naranjo scale to a new one (the Sharma-Nookala-Gota – SNG algorithm) to address these shortcomings. We piloted the SNG causality assessment algorithm in patients suffering from AEs due to various drugs. The SNG algorithm was found to have good concordance with the physicians’ assessment of causality. As a next step, we validated the SNG algorithm in patients receiving a standard drug combination of pemetrexed and carboplatin for lung cancer combination. Out of the 104 AEs observed in 65 patients, the SNG causality assessment algorithm showed good concordance (except in two cases) with the physicians’ decision of causality assessment, while the Naranjo algorithm was not so successful. Hence, the SNG algorithm can be a better guide for causality assessment of AEs.

Published
2021
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39. A Limited Sampling Strategy for Therapeutic Drug Monitoring of Mycophenolate Mofetil for Prophylaxis of Acute Graft-Versus-Host Disease in Allogeneic Stem Cell Transplantation

Author

Gota, Vikram, Purohit, Vaitashi, Gurjar, Murari, Nayak, Lingaraj, Punatar, Sachin, Gokarn, Anant, Bonda, Avinash, Bagal, Bhausaheb, Vora, Chakor Sunil, Patil, Anand, Nookala, Manjunath, and Khattry, Navin

Abstract

A universally accepted strategy for therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) in the prevention of acute graft-versus-host disease (aGVHD) in allogenic hematopoietic stem cell transplantation (alloHSCT) does not exist. We explored the feasibility of developing a limited sampling strategy (LSS) for TDM of MMF in this setting. Patients undergoing alloHSCT received standard MMF-cyclosporine prophylaxis, with MMF administered twice daily (BD) for matched transplant recipients or thrice daily (TID) in haploidentical transplantation. Intensive blood sampling was carried out on day 7 and area under the concentration–time curve (AUC) of mycophenolic acid (MPA), the active metabolite, was estimated using noncompartmental analysis. The ability of MPA exposure defined by AUC0-12to discriminate between responders (patients who did not develop GVHD) and nonresponders (patients who developed GVHD) was determined by receiver operating characteristic curve analysis. Patients were divided into training and validation sets within BD and TID groups. Mathematical equations were developed from the training set to predict AUC0-12from an abbreviated AUC involving a limited number of sampling points. The equations were validated in the validation set by comparing the MPA AUC0-12predicted from LSS with the observed AUC0-12. It was observed that patients with AUC0-12≤18.99 mg*h/L had a higher risk of developing aGVHD [odds ratio (OR) = 2.63 (1.17 to 5.87), P= 0.06]. The benefit was more in matched transplant recipients [OR = 3.5 (1.30 to 9.49), P= 0.05] as compared to haploindentical transplant [OR = 2.8 (0.49 to 15.91), P= NS]. Using the mathematical equations, the observed AUC0-12was predicted with 92.31% accuracy in the BD subset and 100% accuracy in the TID subset for a combined accuracy of 94.76%. A set of just three samples that constituted the abbreviated AUC1-4was used to develop the predictive models. The LSS could be employed for the therapeutic monitoring of MMF particularly in patients undergoing matched hematopoietic stem cell transplantation.

Published
2020
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40. Opioid antidote induced pulmonary edema and lung injury.

Author

Yarlagadda, Keerthi, Kim, Jinah, Kanderi, Tejaswi, Sendil, Selin, and Nookala, Vinod Kumar

Abstract

Opioid overdose emergencies are increasing every year, naloxone is the antidote for the treatment of opioid overdose. Naloxone is being dispensed to even lay persons through some programs to prevent opioid overdose deaths. 23 year old patient presented with naloxone treated opioid overdose complained of chest pain, pink frothy sputum production and shortness of breath. Physical exam showed tachycardia, tachypnea and coarse breath sounds. Imaging of the lungs showed diffuse pulmonary edema. Within an hour after the administration of naloxone patient developed pulmonary edema and lung injury. Patient was managed with non-invasive positive pressure ventilation which improved patient's symptoms in less than 6 hours confirmed by radiological improvement in 24–36 hrs. There are no specific observation guidelines post naloxone treatment in opiate overdose patients. We recommend early treatment of naloxone induced pulmonary complications during the observation period with non-invasive positive pressure ventilation to reduce the morbidity. [ABSTRACT FROM AUTHOR]

Published
2020
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41. Heterogeneity in FoxP3- and GARP/LAP-Expressing T Regulatory Cells in an HLA Class II Transgenic Murine Model of Necrotizing Soft Tissue Infections by Group A Streptococcus

Author

Nookala, Suba, Mukundan, Santhosh, Fife, Alexander, Alagarsamy, Jeyashree, and Kotb, Malak

Abstract

Invasive group A streptococcus (GAS) infections include necrotizing soft tissue infections (NSTI) and streptococcal toxic shock syndrome (STSS). We have previously shown that host HLA class II allelic variations determine the risk for necrotizing fasciitis (NF), a dominant subgroup of NSTI, and STSS by modulating responses to GAS superantigens (SAgs).

Published
2018
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45. Passive proton therapy vs. IMRT planning study with focal boost for prostate cancer.

Author

Yeo I, Nookala P, Gordon I, Schulte R, Barnes S, Ghebremedhin A, Wang N, Yang G, Ling T, Bush D, Slater J, and Patyal B

Subjects
Humans, Male, Radiotherapy Dosage, Prostatic Neoplasms radiotherapy, Proton Therapy methods, Radiotherapy Planning, Computer-Assisted methods, Radiotherapy, Conformal methods, Radiotherapy, Intensity-Modulated methods
Abstract

Background: Exploiting biologic imaging, studies have been performed to boost dose to gross intraprostatic tumor volumes (GTV) while reducing dose elsewhere in the prostate. Interest in proton beams has increased due to superior normal-tissue sparing they afford. Our goal was to dosimetrically compare 3D conformal proton boost plans with intensity-modulated radiation therapy (IMRT) plans with respect to target coverage and avoiding organs at risk., Methods: Treatment planning computer tomography scans of ten patients were selected. For each patient, two hypothetical but realistic GTVs each with a fixed volume were contoured in different anatomical locations of the prostate. IMRT and proton beam plans were created with a prescribed dose of 50.4 Gy to the initial planning target volume (PTV) including the PTV of the seminal vesicles (PSV), 70.2 Gy to the PTV of the prostate (PPS), and 90 Gy to the PTV of the gross tumor volumes (PGTVs). For proton plans, uncertainties of range and patient setup were accounted for; apertures were adjusted until the dose-volume coverage of PTVs matched that of the IMRT plan. For both plans, prescribed PTV doses were made identical to allow for comparing normal-tissue doses., Results: Protons delivered more homogeneous but less conformal doses to PGTVs than IMRT did and comparable doses to PSV and PPS. Volumes of bladder and rectum receiving doses higher than 65 Gy were similar for both plans. However, volumes receiving less than 65 Gy were significantly reduced, i.e., protons reduced integral dose by 45.6 % and 26.5 % for rectum and bladder, respectively. This volume-sparing was also seen in femoral heads and penile bulb., Conclusions: Protons delivered comparable doses to targets in dose homogeneity and conformity and spared normal tissues from intermediate-to-low doses better than IMRT did. Further improvement of dose sparing and changes in homogeneity and conformity may be achieved by reducing proton range uncertainties and from implementing intensity modulation.

Published
2015
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46. Evaluation of normal tissue exposure in patients receiving radiotherapy for pancreatic cancer based on RTOG 0848.

Author

Ling TC, Slater JM, Mifflin R, Nookala P, Grove R, Ly AM, Patyal B, Slater JD, and Yang GY

Abstract

Background: Pancreatic cancer is a highly aggressive malignancy. Chemoradiotherapy (CRT) is utilized in many cases to improve locoregional control; however, toxicities associated with radiation can be significant given the location of the pancreas. RTOG 0848 seeks to evaluate chemoradiation using either intensity-modulated radiation therapy (IMRT) or 3D conformal photon radiotherapy (3DCRT) modalities as an adjuvant treatment. The purpose of this study is to quantify the dosimetric changes seen when using IMRT or 3D CRT photon modalities, as well as proton radiotherapy, in patients receiving CRT for cancer of the pancreas treated per RTOG 0848 guidelines., Materials: Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using IMRT and 3DCRT as well as proton radiotherapy were created for each patient. All planning volumes were created per RTOG 0848 protocol. Dose-volume histograms (DVH) were calculated and analyzed in order to compare plans between the three modalities. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord., Results: There was no difference between the IMRT and 3DCRT plans in dose delivered to the kidneys, liver, or bowel. The proton radiotherapy plans were found to deliver lower mean total kidney doses, mean liver doses, and liver D1/3 compared to the IMRT plans. The proton plans also gave less mean liver dose, liver D1/3, bowel V15, and bowel V50 in comparison to the 3DCRT., Conclusions: For patients receiving radiotherapy per ongoing RTOG 0848 for pancreatic cancer, there was no significant difference in normal tissue sparing between IMRT and 3DCRT treatment planning. Therefore, the choice between the two modalities should not be a confounding factor in this study. The proton plans also demonstrated improved OAR sparing compared to both IMRT and 3DCRT treatment plans.

Published
2015
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