Jaspreet Pannu

All Publications

• Threat Net: A Metagenomic Surveillance Network for Biothreat Detection and Early Warning. Health security Sharma, S., Pannu, J., Chorlton, S., Swett, J. L., Ecker, D. J. 2023

  Abstract

  Early detection of novel pathogens can prevent or substantially mitigate biological incidents, including pandemics. Metagenomic next-generation sequencing (mNGS) of symptomatic clinical samples may enable detection early enough to contain outbreaks, limit international spread, and expedite countermeasure development. In this article, we propose a clinical mNGS architecture we call "Threat Net," which focuses on the hospital emergency department as a high-yield surveillance location. We develop a susceptible-exposed-infected-removed (SEIR) simulation model to estimate the effectiveness of Threat Net in detecting novel respiratory pathogen outbreaks. Our analysis serves to quantify the value of routine clinical mNGS for respiratory pandemic detection by estimating the cost and epidemiological effectiveness at differing degrees of hospital coverage across the United States. We estimate that a biological threat detection network such as Threat Net could be deployed across hospitals covering 30% of the population in the United States. Threat Net would cost between $400 million and $800 million annually and have a 95% chance of detecting a novel respiratory pathogen with traits of SARS-CoV-2 after 10 emergency department presentations and 79 infections across the United States. Our analyses suggest that implementing Threat Net could help prevent or substantially mitigate the spread of a respiratory pandemic pathogen in the United States.

  View details for DOI 10.1089/hs.2022.0160

  View details for PubMedID 37367195

• Zero In on Pandemic Prevention ISSUES IN SCIENCE AND TECHNOLOGY Pannu, J., Schmitt, J., Swett, J. 2023; 39 (4): 54-57

  View details for Web of Science ID 001123597400011

• Programmable Antivirals and Just-in-Time Vaccines: Biosecurity Implications of Viral RNA Secondary Structure Targeting. Health security Pannu, J., Glenn, J. S. 2022

  View details for DOI 10.1089/hs.2022.0098

  View details for PubMedID 36576394

• Strengthen oversight of risky research on pathogens. Science (New York, N.Y.) Pannu, J., Palmer, M. J., Cicero, A., Relman, D. A., Lipsitch, M., Inglesby, T. 2022: eadf6020

  Abstract

  Policy reset and convergence on governance are needed.

  View details for DOI 10.1126/science.adf6020

  View details for PubMedID 36480598

• Protocols and risks: when less is more. Nature protocols Pannu, J., Sandbrink, J. B., Watson, M., Palmer, M. J., Relman, D. A. 2021

  View details for DOI 10.1038/s41596-021-00655-6

  View details for PubMedID 34873329

• Global health security as it pertains to Zika, Ebola, and COVID-19. Current opinion in infectious diseases Pannu, J., Barry, M. 2021

  Abstract

  PURPOSE OF REVIEW: Due to the impact of the COVID-19 pandemic this past year, we have witnessed a significant acceleration in the science, technology, and policy of global health security. This review highlights important progress made toward the mitigation of Zika, Ebola, and COVID-19 outbreaks. These epidemics and their shared features suggest a unified policy and technology agenda that could broadly improve global health security.RECENT FINDINGS: Molecular epidemiology is not yet in widespread use, but shows promise toward informing on-the-ground decision-making during outbreaks. Point-of-care (POC) diagnostics have been achieved for each of these threats; however, deployment of Zika and Ebola diagnostics lags behind those for COVID-19. POC metagenomics offers the possibility of identifying novel viruses. Vaccines have been successfully approved for Ebola and COVID-19, due in large part to public-private partnerships and advance purchase commitments. Therapeutics trials conducted during ongoing epidemics have identified effective antibody therapeutics for Ebola, as well as steroids (both inhaled and oral) and a broad-spectrum antiviral for COVID-19.SUMMARY: Achieving global health security remains a challenge, though headway has been made over the past years. Promising policy and technology strategies that would increase resilience across emerging viral pathogens should be pursued.

  View details for DOI 10.1097/QCO.0000000000000775

  View details for PubMedID 34334661

• Hydrogen Peroxide Methods for Decontaminating N95 Filtering Facepiece Respirators APPLIED BIOSAFETY Rempel, D., Henneman, J., Agalloco, J., Crittenden, J., N95DECON Consortium 2021; 26 (2): 71-79

  Abstract

  Introduction: During a pandemic, when the supply of N95 filtering facepiece respirators (FFRs) is limited, FFRs may be decontaminated by methods that inactivate pathogens as long as they do not damage FFR function. Hydrogen peroxide (H2O2) is widely used for decontamination in medical settings. Objective: To review the literature on the use of H2O2 to decontaminate N95 FFRs and identify methods that inactivate virus and preserve FFR filtration efficiency and fit. Methods: The literature was searched for studies evaluating H2O2 decontamination methods on inactivating SARS-CoV-2 and other viruses and microorganisms inoculated on N95 FFRs and the effects on respirator filtration efficiency and fit. Current U.S. Federal guidelines are also presented. Results: Findings from relevant laboratory studies (N = 24) are summarized in tables. Commercially available H2O2 decontamination systems differ on how H2O2 is delivered, the temperature, the duration of treatment, and other factors that can impact N95 FFR filtration efficiency and fit. Some methods inactivate SARS-CoV-2 virus-contaminated N95 FFRs with >3 log attenuation, whereas other methods are yet to be evaluated. Discussion and Conclusion: Most of the H2O2 methods reviewed effectively decontaminate N95 FFRs without damaging FFR function. However, some methods adversely impact N95 fit or filtration efficiency, which could go undetected by the end user and compromise their protection from pathogen inhalation. When making decisions about H2O2 decontamination of respirators, it is important to understand differences in methods, effects on different FFR models, and potential hazards to workers who manage the decontamination process.

  View details for DOI 10.1089/apb.20.0042

  View details for Web of Science ID 000662962500004

  View details for PubMedID 36034688

  View details for PubMedCentralID PMC9134325

• Current Understanding of Ultraviolet-C Decontamination of N95 Filtering Facepiece Respirators. Applied biosafety : journal of the American Biological Safety Association Grist, S. M., Geldert, A., Gopal, A., Su, A., Balch, H. B., Herr, A. E. 2021; 26 (2): 90-102

  Abstract

  Introduction: The COVID-19 pandemic has led to critical shortages of single-use N95 filtering facepiece respirators. The US Centers for Disease Control and Prevention has identified ultraviolet-C (UV-C) irradiation as one of the most promising decontamination methods during crisis-capacity surges; however, understanding the mechanism of pathogen inactivation and post-treatment respirator performance is central to effective UV-C decontamination. Objective: We summarize the UV-C N95 decontamination evidence and identify key metrics. Methods: We evaluate the peer-reviewed literature on UV-C decontamination to inactivate SARS-CoV-2, viral analogues, and other microorganisms inoculated on N95s, as well as the resulting effect on respirator fit and filtration. Where peer-reviewed studies are absent, we discuss outstanding questions and ongoing work. Key Findings: Evidence supports that UV-C exposure of ≥1.0 J/cm2 inactivates SARS-CoV-2 analogues (≥3-log reduction) on the majority of tested N95 models. The literature cautions that (1) viral inactivation is N95 model-dependent and impeded by shadowing, (2) N95 straps require secondary decontamination, (3) higher doses may be necessary to inactivate other pathogens (e.g., some bacterial spores), and (4) while N95 fit and filtration appear to be preserved for 10-20 cycles of 1.0 J/cm2, donning and doffing may degrade fit to unacceptable levels within fewer cycles. Results and Discussion: Effective N95 UV-C treatment for emergency reuse requires both (1) inactivation of the SARS-CoV-2 virus, achieved through application of UV-C irradiation at an appropriate wavelength and effective dose, and (2) maintenance of the fit and filtration efficiency of the N95. Conclusions: UV-C treatment is a risk-mitigation process that should be implemented only under crisis-capacity conditions and with proper engineering, industrial hygiene, and biosafety controls.

  View details for DOI 10.1089/apb.20.0051

  View details for PubMedID 36034687

  View details for PubMedCentralID PMC9134326

• Room Temperature Wait and Reuse for Bioburden Reduction of SARS-CoV-2 on N95 Filtering Facepiece Respirators APPLIED BIOSAFETY Smullin, S. J., Tarlow, B. D., N95DECON Consortium 2021; 26 (2): 103-111

  View details for DOI 10.1089/apb.20.0055

  View details for Web of Science ID 000662962500007

• The state inoculates: vaccines as soft power. The Lancet. Global health Pannu, J., Barry, M. 2021

  View details for DOI 10.1016/S2214-109X(21)00091-7

  View details for PubMedID 33713632

• Inclusive Biomedical Innovation during the COVID-19 Pandemic GLOBAL POLICY Pannu, J. 2020

  View details for DOI 10.1111/1758-5899.12876

  View details for Web of Science ID 000577666900001

• Inclusive Biomedical Innovation during the COVID-19 Pandemic. Global policy Pannu, J. 2020

  Abstract

  CEPI represents the first step towards Joseph Stiglitz's vision, cited by Gubby, of a fund which provides large rewards for cures to common diseases such as malaria, and smaller rewards for rarer diseases or less innovative 'me-too' drugs (Stiglitz, BMJ, 333, 2006, pp. 1279-1280). As a fledgling organization facing a Goliath, it deserves international support in its dual goals of incentivizing innovation and ensuring equitable access to biomedical advances.

  View details for DOI 10.1111/1758-5899.12876

  View details for PubMedID 33230401

  View details for PubMedCentralID PMC7675476

• Scientific Collaboration During the COVID-19 Pandemic: N95DECON.org ANNALS OF WORK EXPOSURES AND HEALTH Rempel, D., N95DECON Consortium 2020; 64 (8): 775-777

  Abstract

  Many academics and researchers have responded to the COVID-19 pandemic by forming on-line national and international collaborative groups to rapidly investigate issues of prevention and treatment. This commentary describes the spontaneous formation of an international team of 115 researchers who summarized the literature on safe methods for decontaminating N95 filtering facepiece respirators in response to the supply crisis. The summary reports and fact sheets on the (www.n95decon.org) website have had more than 200 000 unique visits and the organization's webinars have reached health care professionals from more than 50 countries. The team is extending its mission to cover other personal protective equipment. The success of these collaborations may alter how scientific questions are tackled in the future.

  View details for DOI 10.1093/annweh/wxaa057

  View details for Web of Science ID 000607031100001

  View details for PubMedID 32533166

  View details for PubMedCentralID PMC7314228

• Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings-International Travel-Related Measures. Emerging infectious diseases Pannu, J. n. 2020; 26 (9)

  View details for DOI 10.3201/eid2609.201990

  View details for PubMedID 32491981

• Running ahead of pandemics: achieving in-advance antiviral drugs SSRN Pannu, J. 2020

  View details for DOI 10.2139/ssrn.3570737

• Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. The American journal of psychiatry Williams, N. R., Heifets, B. D., Blasey, C., Sudheimer, K., Pannu, J., Pankow, H., Hawkins, J., Birnbaum, J., Lyons, D. M., Rodriguez, C. I., Schatzberg, A. F. 2018: appiajp201818020138

  Abstract

  OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects.METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1.RESULTS: In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis.CONCLUSIONS: The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.

  View details for PubMedID 30153752

• High-Dose Theta-Burst Transcranial Magnetic Stimulation Modulates Heart Rate Variability Pannu, J., Kallioniemi, E., Gulser, M., Stimpson, K., DeSouza, D., Sudheimer, K., Williams, N. ELSEVIER SCIENCE INC. 2018: S189

  View details for Web of Science ID 000432466300472

• High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain : a journal of neurology Williams, N. R., Sudheimer, K. D., Bentzley, B. S., Pannu, J. n., Stimpson, K. H., Duvio, D. n., Cherian, K. n., Hawkins, J. n., Scherrer, K. H., Vyssoki, B. n., DeSouza, D. n., Raj, K. S., Keller, J. n., Schatzberg, A. F. 2018

  View details for PubMedID 29415152

• Transcranial Magnetic Stimulation for Disorders Other Than Depression TRANSCRANIAL MAGNETIC STIMULATION: CLINICAL APPLICATIONS FOR PSYCHIATRIC PRACTICE Pannu, J., DeSouza, D. D., Samara, Z., Raj, K. S., Williams, N. R., Lanocha, K. I., Bermudes, R. A., Lanocha, K. I., Janicak, P. G. 2018: 157–72

  View details for Web of Science ID 000549755600010

• Unilateral ultra-brief pulse electroconvulsive therapy for depression in Parkinson's disease ACTA NEUROLOGICA SCANDINAVICA Williams, N. R., Bentzley, B. S., Sahlem, G. L., Pannu, J., Korte, J. E., Revuelta, G., Short, E. B., George, M. S. 2017; 135 (4): 407-411

  Abstract

  Electroconvulsive therapy (ECT) has demonstrated efficacy in treating core symptoms of Parkinson's disease (PD); however, widespread use of ECT in PD has been limited due to concern over cognitive burden. We investigated the use of a newer ECT technology known to have fewer cognitive side effects (right unilateral [RUL] ultra-brief pulse [UBP]) for the treatment of medically refractory psychiatric dysfunction in PD.This open-label pilot study included 6 patients who were assessed in the motoric, cognitive, and neuropsychiatric domains prior to and after RUL UBP ECT. Primary endpoints were changes in total score on the HAM-D-17 and GDS-30 rating scales.Patients were found to improve in motoric and psychiatric domains following RUL UBP ECT without cognitive side effects, both immediately following ECT and at 1-month follow-up.This study demonstrates that RUL UBP ECT is safe, feasible, and potentially efficacious in treating multiple domains of PD, including motor and mood, without clear cognitive side effects.

  View details for DOI 10.1111/ane.12614

  View details for Web of Science ID 000398035900004

  View details for PubMedCentralID PMC5133197

• It takes time to tune ANNALS OF TRANSLATIONAL MEDICINE Bentzley, B. S., Pannu, J., Badran, B. W., Halpern, C. H., Williams, N. R. 2017; 5 (7): 171

  View details for PubMedID 28480207

  View details for PubMedCentralID PMC5401673

• Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation NEUROCASE Williams, N. R., Sahlem, G., Pannu, J., Takacs, I., Short, B., Revuelta, G., George, M. S. 2017; 23 (1): 26-30

  Abstract

  Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

  View details for DOI 10.1080/13554794.2016.1276605

  View details for Web of Science ID 000399644200005

  View details for PubMedID 28376692

• Bridging to deep brain stimulation implantation using electroconvulsive therapy in Parkinson’s disease BRAIN STIMULATION Williams, N., Sahlem, G., Pannu, J., Takacs, I., Short, B., Revuelta, G., George, M. 2017

  View details for DOI 10.1016/j.brs.2017.01.242

• Optimization of epidural cortical stimulation for treatment-resistant depression. Brain stimulation Williams, N. R., Bentzley, B. S., Hopkins, T. n., Pannu, J. n., Sahlem, G. L., Takacs, I. n., George, M. S., Nahas, Z. n., Short, E. B. 2017

  View details for PubMedID 28918944

• Assessing Screening Guidelines for Cardiovascular Disease Risk Factors using Routinely Collected Data. Scientific reports Pannu, J. n., Poole, S. n., Shah, N. n., Shah, N. H. 2017; 7 (1): 6488

  Abstract

  This study investigates if laboratory data can be used to assess whether physician-retesting patterns are in line with established guidelines, and if these guidelines identify deteriorating patients in a timely manner. A total of 7594 patients with high cholesterol were studied, along with 2764 patients with diabetes. More than 90% of borderline high cholesterol patients are retested within the 3 year recommended period, however less than 75% of pre-diabetic patients have repeated tests within the suggested 1-year time frame. Patients with borderline high cholesterol typically progress to full high cholesterol in 2-3 years, and pre-diabetic patients progress to full diabetes in 1-2 years. Data from routinely ordered laboratory tests can be used to monitor adherence to clinical guidelines. These data may also be useful in the design of adaptive testing strategies that reduce unnecessary testing, while ensuring that patient deterioration is identified in a timely manner. Established guidelines for testing of total serum cholesterol for hypercholesterolemia are appropriate and are well-adhered to, whereas guidelines for glycated hemoglobin A1c testing for type 2 diabetes mellitus could be improved to bring them in line with current practice and avoid unnecessary testing.

  View details for PubMedID 28747722

• Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression Journal of Visualized Experiments Williams, N., Pannu, J., Bentzley, B., Hopkins, T., Badran, B., Short, E., George, M., Takacs, I., Nahas, Z. 2017
• Five Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression BRAIN STIMULATION Williams, N. R., Short, E. B., Hopkins, T., Bentzle, B. S., Sahlem, G. L., Pannu, J., Schmidt, M., Borckardt, J. J., Korte, J. E., George, M. S., Takacs, I., Nahas, Z. 2016; 9 (6): 897-904

  Abstract

  Epidural prefrontal cortical stimulation (EpCS) represents a novel therapeutic approach with many unique benefits that can be used for treatment-resistant depression (TRD).To examine the long-term safety and efficacy of EpCS of the frontopolar cortex (FPC) and dorsolateral prefrontal cortex (DLPFC) for treatment of TRD.Adults (N = 5) who were 21-80 years old with severe TRD [failure to respond to adequate courses of at least 4 antidepressant medications, psychotherapy and ≥20 on the Hamilton Rating Scale for Depression (HRSD24)] were recruited. Participants were implanted with bilateral EpCS over the FPC and DLPFC and received constant, chronic stimulation throughout the five years with Medtronic IPGs. They were followed for 5 years (2/1/2008-10/14/2013). Efficacy of EpCS was assessed with the HRSD24 in an open-label design as the primary outcome measure at five years.All 5 patients continued to tolerate the therapy. The mean improvements from pre-implant baseline on the HRSD24 were [7 months] 54.9% (±37.7), [1 year] 41.2% (±36.6), [2 years] 53.8% (±21.7), and [5 years] 45% (±47). Three of 5 (60%) subjects continued to be in remission at 5 years. There were 5 serious adverse events: 1 electrode 'paddle' infection and 4 device malfunctions, all resulting in suicidal ideation and/or hospitalization.These results suggest that chronic bilateral EpCS over the FPC and DLPFC is a promising and potentially durable new technology for treating TRD, both acutely and over 5 years.

  View details for DOI 10.1016/j.brs.2016.06.054

  View details for Web of Science ID 000387197500013

  View details for PubMedID 27443912

• Stimulating Across the Frontostriatal Circuitry to Treat Parkinson's Disease Williams, N. R., Short, E., Bentzley, B., Pannu, J., Sahlem, G., Hanlon, C., Korte, J., Revuelta, G., George, M. ELSEVIER SCIENCE INC. 2016: 402S–403S

  View details for Web of Science ID 000432440805134

• Ubiquitin Specific Protease 21 Is Dispensable for Normal Development, Hematopoiesis and Lymphocyte Differentiation PLOS ONE Pannu, J., Belle, J. I., Foerster, M., Duerr, C. U., Shen, S., Kane, L., Harcourt, K., Fritz, J. H., Clare, S., Nijnik, A. 2015; 10 (2)

  Abstract

  USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.

  View details for DOI 10.1371/journal.pone.0117304

  View details for Web of Science ID 000350682600061

  View details for PubMedID 25680095

  View details for PubMedCentralID PMC4332479