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1. Deep Neural Network (DNN) for Water/Fat Separation: Supervised Training, Unsupervised Training, and No Training

Author

Jafari, R., Spincemaille, P., Zhang, J., Nguyen, T. D., Prince, M. R., Luo, X., Cho, J., Margolis, D., and Wang, Y.

Subjects
Electrical Engineering and Systems Science - Image and Video Processing, Computer Science - Computer Vision and Pattern Recognition
Abstract

Purpose: To use a deep neural network (DNN) for solving the optimization problem of water/fat separation and to compare supervised and unsupervised training. Methods: The current T2*-IDEAL algorithm for solving fat/water separation is dependent on initialization. Recently, deep neural networks (DNN) have been proposed to solve fat/water separation without the need for suitable initialization. However, this approach requires supervised training of DNN (STD) using the reference fat/water separation images. Here we propose two novel DNN water/fat separation methods 1) unsupervised training of DNN (UTD) using the physical forward problem as the cost function during training, and 2) no-training of DNN (NTD) using physical cost and backpropagation to directly reconstruct a single dataset. The STD, UTD and NTD methods were compared with the reference T2*-IDEAL. Results: All DNN methods generated consistent water/fat separation results that agreed well with T2*-IDEAL under proper initialization. Conclusion: The water/fat separation problem can be solved using unsupervised deep neural networks., Comment: 19 pages, 5 figures

Published
2020

2. Correction: Diffusion-Weighted Imaging in Cancer: Physical Foundations and Applications of Restriction Spectrum Imaging

Author

White, NS, McDonald, C, Farid, N, Kuperman, J, Karow, D, Schenker-Ahmed, NM, Bartsch, H, Rakow-Penner, R, Holland, D, Shabaik, A, Bjørnerud, A, Hope, T, Hattangadi-Gluth, J, Liss, M, Parsons, JK, Chen, CC, Raman, S, Margolis, D, Reiter, RE, Marks, L, Kesari, S, Mundt, AJ, Kane, CJ, Carter, BS, Bradley, WG, and Dale, AM

Subjects
Oncology and Carcinogenesis, Oncology & Carcinogenesis
Published
2014

3. Erratum: Diffusion-Weighted imaging in cancer: Physical foundations and applications of restriction spectrum imaging (Cancer Research (2014) 74 (4638-4652))

Author

White, NS, McDonald, C, Farid, N, Kuperman, J, Karow, D, Schenker-Ahmed, NM, Bartsch, H, Rakow-Penner, R, Holland, D, Shabaik, A, Bjørnerud, A, Hope, T, Hattangadi-Gluth, J, Liss, M, Parsons, JK, Chen, CC, Raman, S, Margolis, D, Reiter, RE, Marks, L, Kesari, S, Mundt, AJ, Kane, CJ, Carter, BS, Bradley, WG, and Dale, AM

Subjects
Oncology & Carcinogenesis, Oncology and Carcinogenesis
Published
2014

9. Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Author

Harper, J, Betts, MR, Lichterfeld, M, Müller-Trutwin, M, Margolis, D, Bar, KJ, Li, JZ, McCune, JM, Lewin, S, Kulpa, D, Diallo, DD, Lederman, MM, Paiardini, M, Harper, J, Betts, MR, Lichterfeld, M, Müller-Trutwin, M, Margolis, D, Bar, KJ, Li, JZ, McCune, JM, Lewin, S, Kulpa, D, Diallo, DD, Lederman, MM, and Paiardini, M

Abstract

Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2]), ART alone is incapable of eradicating the "reservoir" of resting, latently infected CD4+ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS' 95-95-95 targets) [6-8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a "cure" remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by Pathogens and Immunity in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure

Published
2023

10. Erratum to: Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Author

Harper, J, Betts, MR, Lichterfeld, M, Müller-Trutwin, M, Margolis, D, Bar, KJ, Li, JZ, McCune, JM, Lewin, SR, Kulpa, D, Ávila-Ríos, S, Diallo, DD, Lederman, MM, Paiardini, M, Harper, J, Betts, MR, Lichterfeld, M, Müller-Trutwin, M, Margolis, D, Bar, KJ, Li, JZ, McCune, JM, Lewin, SR, Kulpa, D, Ávila-Ríos, S, Diallo, DD, Lederman, MM, and Paiardini, M

Abstract

[This corrects the article DOI: 10.20411/pai.v8i2.665.].

Published
2023

11. A trip down memory lane with Retrovirology

Author

Benkirane, Monsef, Berkhout, Ben, Borrow, Persephone, Fassati, Ariberto, Fujii, Masahiro, Garcia-Martinez, J. Victor, Margolis, D., Nijhuis, Monique, Parent, Leslie, Strebel, Klaus, Venter, François, Kirchhoff, Frank, Lever, Andrew, Ross, Susan, and Mak, Johnson

Published
2019
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12. Highlights from the Tenth International Workshop on HIV Persistence during Therapy, December, 13th-16th 2022, Miami, Florida – USA

Author

Archin, N., primary, Bar, K.J., additional, Burdo, T., additional, Caskey, M., additional, Chahroudi, A., additional, Farzan, M., additional, Ho, Y.-C., additional, Jones, R.B., additional, Kearney, Mary, additional, Kuritzkes, D., additional, Margolis, D., additional, Martinez-Picado, J., additional, Okoye, A., additional, Salgado, M., additional, and Stevenson, Mario, additional

Published
2023
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20. Distribution of long-acting (LA) cabotegravir (CAB) in plasma, mucosal tissues, and associated fluids after a single ultrasound-guided intramuscular (IM) injection in healthy adult participants

Author

Weld, E., Shaik, J. Sadik, Edick, S., Fuchs, E., Riddler, S., Marzinke, M., D'Amico, R., Bakshi, K., Lou, Y., Hendrix, C.W., Han, K., Ford, S.L., Margolis, D., Spreen, W., and Patel, P.

Subjects
Antiviral agents -- Testing, Anti-HIV agents -- Testing, Ultrasonics in medicine, Injections, Intramuscular -- Testing, Integrase inhibitors -- Testing, Health
Abstract

Background: CAB LA dosed at 2-month intervals demonstrated viro-logic efficacy in maintaining HIV-1 suppression as part of a dual regimen with rilpivirine LA and is undergoing Phase 3 evaluation as a single agent for HIV-1 pre-exposure prophylaxis (PrEP). CAB pharma-cokinetics (PK) in plasma and mucosal tissues associated with sexual HIV-1 transmission were evaluated following single CAB LA IM injection. Methods: Participants received 4 weeks of daily oral CAB 30 mg, followed by 14 to 42 day washout and a single ultrasound-guided gluteal IM injection of CAB LA 600 mg (3 mL). PK samples were collected after oral dosing and through 12 weeks post-injection in plasma, rectal tissue (RT), cervical tissue (CT), vaginal tissue (VT), cervicovaginal fluid (CF), and rectal fluid (RF). CAB concentrations were determined by HPLC-MS/MS. PK parameters were estimated using noncompartmental analysis. Pearson correlations of time-matched tissue and plasma concentration pairs were determined. Results: Nineteen participants (10F, 9M) enrolled with mean age 33 years, weight 79.4 kg, and BMI 27.2 kg/[m.sup.2]. Two participants withdrew before injections, one did not undergo tissue sampling, and one was hospitalized for unrelated serotonin syndrome. Median CAB concentration-time profiles are presented by matrix (Figure 1). Median CAB tissue:plasma ratio was 9% to 10% in RT (r = 0.96), 14% to 18% in CT (r = 0.94), 14% to 16% in VT (r = 0.92), 8% to 13% in CF (r = 0.65), 32% to 45% in RF (r = 0.19). Geometric mean (CVb%) plasma half-life was 19.1 (81.4%) days. Conclusions: Plasma CAB PK was consistent with prior studies, and CAB concentrations in tissue and fluid were proportional to plasma over time. Correlations with plasma concentrations were stronger for tissue (RT, CT, VT) than for luminal fluid (CF and RF). Tissue concentrations were 1/6th (CT, VT) to 1/10th (RT) of plasma concentrations. With sufficient distribution into mucosal tissues associated with sexual HIV-1 transmission, CAB tissue:plasma ratios may serve as important measurements in evaluating CAB LA as an effective PrEP agent., OA04.03 E. Weld (1); J. Sadik Shaik (2); S. Edick (3); E. Fuchs (4); S. Riddler (3); M. Marzinke (1); R. D'Amico (5); K. Bakshi (2); Y. Lou (6); C.W. [...]

Published
2021
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24. A Bond Graph Representation of the Sagittal Spine for Estimation of Ride Comfort

Author

Ali Akbari and Margolis, D.

Subjects
Sagittal Spine, Biomechanics, Ride Comfort, Bond Graphs, human activities
Abstract

Biomechanical models are widely used in rehabilitation, posture prediction studies, and for injury risk assessment (Gatton, Pearcy, and Pettet 2011). With ride comfort becoming important to vehicle manufacturers, there’s a demand for a universal, quantitative ride comfort metric (Da Silva 2002). Mechanical inputs from the ride to the passenger body could cause discomfort (ISO 1997) and the dominant discomfort-causing motions lie in the body’s sagittal plane (longitudinal plane dividing a symmetrical body into left and right sections) (Kozawa, Sugimoto, and Suzuki 1986). This paper develops a biomechanical model of the sagittal spine using bond graphs. The model is computationally cost-effective as it employs fewer degrees of freedom than available models (Bazrgari, Shirazi-Adl, and Arjmand 2007; Amiri, Naserkhaki, and Parnianpour 2019) and is capable of estimating internal loads and displacements with sufficient accuracy. The model could be used for spinal load assessments and ride comfort studies in vehicle dynamics.

Published
2021

27. 'I feel empowered': women's perspectives on and experiences with long-acting injectable antiretroviral therapy in the USA and Spain

Author

Mantsios A, Murray M, Karver TS, Davis W, Margolis D, Kumar P, Swindells S, Bredeek UF, Deltoro MG, García RR, Antela A, Garris C, Shaefer M, Gomis SC, Bernáldez MP, and Kerrigan D

Subjects
antiretroviral therapy, HIV, long-acting injectables, adherence, women
Abstract

Long-acting injectable antiretroviral therapy has been shown to be non-inferior to daily oral antiretroviral therapy in clinical trials and may soon become part of clinical care. While most trial participants to date have been men, approximately one quarter of ongoing Phase 3 trial participants are women offering an important opportunity to understand how long-acting antiretroviral therapy is perceived and experienced by women. We conducted in-depth interviews with 80 people living with HIV participating in Phase 2 and 3 clinical trials of long-acting antiretroviral therapy in the USA and Spain. Fifteen percent (12/80) of trial participants interviewed were women. Interviews were audio-recorded, transcribed and coded using content analysis, focused on gender-specific themes. Women shared many of the positive perceptions expressed by men but also had unique perspectives, including finding that long-acting antiretroviral therapy addressed the challenge of remembering pills amidst busy day-to-day realities including multiple roles and responsibilities, is less time consuming and creates less stress compared to oral antiretroviral therapy, and is emotionally freeing and empowering. The gendered nature of women's lives shaped why and how they were satisfied with long-acting antiretroviral therapy. Findings can inform interventions and support systems to facilitate uptake of and adherence to long-acting antiretroviral therapy in women.

Published
2021

28. Bond Graph Modeling of a Planar Vehicle with Electric Traction Motors for Assisted Torque-Vectoring

Author

Lee, D., Jonathan Loyola, Mccrone, J., and Margolis, D. L.

Subjects
Quantitative Biology::Subcellular Processes, torque distribution, vehicle dynamics, electric vehicle
Abstract

Powertrains for vehicles are transitioning from the internal combustion engine to electric motors. Electric motors have the ability to both output traction and generative braking torque. Furthermore, electric motor powertrains have a smaller size compared to the internal combustion engine powertrain. This opens up thepossibility of different configurations of powertrain layouts. This paper explores an electric vehicle model with motors on both the front and the rear axles. The planar vehicle model with varying motor torque distribution is simulated to validate its handling dynamics.

Published
2021

29. Improved killing of HIV-infected cells by a combination of three neutralizing and non-neutralizing antibodies

Author

Tuyishime, M., Garrido, C., Jha, S., Moeser, M., Mielke, D., Labranche, C., Montefiori, D., Haynes, B.F., Joseph, S., Margolis, D., and Ferrari, G.

Subjects
CD4 lymphocytes -- Health aspects, Monoclonal antibodies -- Health aspects, HIV infection -- Care and treatment, Health
Abstract

Background: Pre-clinical and clinical antibody-dependent cellular cytotoxic (ADCC) responses correlating with protection from HIV-1 infection provide the rationale to leverage them for treatment purposes. We evaluated ADCC mediated by 62 monoclonal antibodies (mAbs) combinations to identify those effective against latent reservoir viruses (LRVs) isolated from ART-suppressed HIV+ donors using Latency Reversing Agents (LRA)-exposed resting latently infected CD4+ T cells. Methods: HIV-1 envelope-specific CD4-binding site CH557, C1/C2 A32, V1/V2 PG9, V3 PGT121, gp120-gp41 interface PGT151 and MPER DH511.2K3 mAbs were tested at a concentration < 1 [micro]g/mL for their ability to mediate ADCC individually and in combinations. Target cells were either primary CD4+ T cells infected in vitro with a panel of 10 clade B LRVs or ART-suppressed HIV+ donor cells exposed to LRAs. We used an Infected Cell Elimination assay and a novel ex vivo modified viral outgrowth assay (Latent Clearance Assay) in presence of autologous primary NK cells, respectively. Results: We observed that within 2 hours of incubation at < 1 [micro]g/mL, 3 mAbs combinations mediated significantly higher killing (p < 0.005) compared to single or paired mAbs. Addition of more than 3 mAbs did not further increase specific killing. A32+ DH511.2K3+ PGT121 was the best combination with a mean of 33.1% ADCC activity. Three LRVs were resistance to neutralization by PGT121, one of which (P800) was also resistant to PG9 and DH511.2K3. The resistance was caused by the escape mutations within HIV-1 Env of these LRVs. These results were confirmed by the loss of the binding of PGT121 and/or DH511.2K3 to cells infected with these LRVs. After 24 hours of incubation, we observed remarkably increased ADCC activity against 4 LRVs tested with the A32+ DH511.2K3+ PGT121 combination, and demonstrated elimination of cells infected with 3-bNAbs-resistant P800 LRV Further, the A32+ DH511.2K3+ PGT121 combination efficiently cleared ex vivo latently infected LRA-treated resting CD4+ T cells from P800 donor by autologous NK cells during a 25-day culture. Conclusions: MAbs combinations targeted the diverse HIV-1 Env epitopes on the surface of infected cells, upon reactivation of the latent infection, more efficiently than individual mAbs. The results strongly indicate the importance of mAb combinations to achieve the broadest activity against HIV-1 infected cells in future cure strategies., OA14.01 M. Tuyishime (1); C. Garrido (2); S. Jha (1); M. Moeser (2); D. Mielke (1); C. LaBranche (1); D. Montefiori (1); B.F. Haynes (3); S. Joseph (4); D. Margolis [...]

Published
2021
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32. 201 A basophil-neuronal axis promotes itch

Author

Wang, F., primary, Trier, A.M., additional, Li, F., additional, Kim, S., additional, Chen, Z., additional, Chai, J., additional, Mack, M., additional, Morrison, S., additional, Hamilton, J.D., additional, Baek, J., additional, Yang, T.B., additional, Heul, A. M. Ver, additional, Xu, A.Z., additional, Xie, Z., additional, Dong, X., additional, Kubo, M., additional, Hu, H., additional, Hsieh, C., additional, Liu, Q., additional, Margolis, D., additional, Ardeleanu, M., additional, Miller, M.J., additional, and Kim, B.S., additional

Published
2021
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34. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

Author

Goggins, M., Overbeek, K.A., Brand, R., Syngal, S., Chiaro, M. del, Bartsch, D.K., Bassi, C., Carrato, A., Farrell, J., Fishman, E.K., Fockens, P., Gress, T.M., Hooft, J.E. van, Hruban, R.H., Kastrinos, F., Klein, A., Lennon, A.M., Lucas, A., Park, W., Rustgi, A., Simeone, D., Stoffel, E., Vasen, H.F.A., Cahen, D.L., Canto, M.I., Bruno, M., Arcidiacono, P.G., Ashida, R., Ausems, M., Besselink, M., Biermann, K., Bonsing, B., Brentnall, T., Chak, A., Early, D., Fernandez-Del Castillo, C., Frucht, H., Furukawa, T., Gallinger, S., Geurts, J., Koerkamp, B.G., Hammel, P., Hes, F., Iglesias-Garcia, J., Kamel, I., Kitano, M., Kloppel, G., Krak, N., Kurtz, R., Kwon, R., Lachter, J., Lee, J., Levy, M., Malleo, G., Meguid, C., Maitra, A., Margolis, D., Offerhaus, J., Olson, S., Paiella, S., Petersen, G., Poley, J.W., Real, F.X., Saltzman, J., Schulick, R., Stoita, A., Takaori, K., Tanaka, M., Tamm, E., Topazian, M., Vazquez-Sequeiros, E., Vleggaar, F., Cappel, W.D.T.N., Yeo, C., Wasser, M., Wagner, A., Wallace, M., Wolfgang, C., Wood, L., Int Canc Pancreas Screening, Goggins, M., Overbeek, K. A., Brand, R., Syngal, S., Del Chiaro, M., Bartsch, D. K., Bassi, C., Carrato, A., Farrell, J., Fishman, E. K., Fockens, P., Gress, T. M., Van Hooft, J. E., Hruban, R. H., Kastrinos, F., Klein, A., Lennon, A. M., Lucas, A., Park, W., Rustgi, A., Simeone, D., Stoffel, E., Vasen, H. F. A., Cahen, D. L., Canto, M. I., Bruno, M, Arcidiacono, P. G., Gastroenterology & Hepatology, Clinical sciences, Medical Genetics, Gastroenterology and Hepatology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, and CCA - Cancer Treatment and Quality of Life

Subjects
Endoscopic ultrasound, medicine.medical_specialty, Biomedical Research, MEDLINE, pancreatic ductal adenocarcinoma, familial pancreatic cancer, Biomedical Research/methods, Article, Germline mutation, Mass Screening/methods, SDG 3 - Good Health and Well-being, Risk Factors, Pancreatic cancer, medicine, Humans, Mass Screening, Pancreatic Neoplasms/diagnosis, Age Factor, Genetic Predisposition to Disease, Family history, Intensive care medicine, early detection, Early Detection of Cancer, Germ-Line Mutation, Medicine(all), Hereditary pancreatitis, medicine.diagnostic_test, business.industry, Carcinoma, Age Factors, Gastroenterology, Pancreatic Neoplasm, Cancer, medicine.disease, Carcinoma/diagnosis, Population Surveillance/methods, Pancreatic Neoplasms, medicine.anatomical_structure, Population Surveillance, surveillance, Early Detection of Cancer/methods, business, Pancreas, genetic predisposition, Human
Abstract

Background and aimThe International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals).MethodsA modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed.ResultsConsensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions.ConclusionsPancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.

Published
2020

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