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1. Challenges with sirolimus experimental data to inform QSP model of post‐transplantation cyclophosphamide regimens

Author

Mohanan, Ezhilpavai, Shen, Guofang, Ren, Suping, Fan, Hsuan‐Hao, Moua, Kao Tang Ying, Karolak, Aleksandra, Rockne, Russell C, Nakamura, Ryotaro, Horne, David A, Kanakry, Christopher G, Mager, Donald E, and McCune, Jeannine S

Subjects
Biomedical and Clinical Sciences, Immunology, Transplantation, Cancer, Prevention, Rare Diseases, Humans, Sirolimus, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Immunosuppressive Agents, T-Lymphocytes, Regulatory, Animals, Models, Biological, Cardiorespiratory Medicine and Haematology, Oncology and Carcinogenesis, Other Medical and Health Sciences, General Clinical Medicine, Cardiovascular medicine and haematology, Pharmacology and pharmaceutical sciences
Abstract

Dose optimization of sirolimus may further improve outcomes in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD). Sirolimus exposure-response association studies in HCT patients (i.e., the association of trough concentration with clinical outcomes) have been conflicting. Sirolimus has important effects on T-cells, including conventional (Tcons) and regulatory T-cells (Tregs), both of which have been implicated in the mechanisms by which PTCy prevents GVHD, but there is an absence of validated biomarkers of sirolimus effects on these cell subsets. Considering the paucity of existing biomarkers and the complexities of the immune system, we conducted a literature review to inform a quantitative systems pharmacology (QSP) model of GVHD. The published literature presented multiple challenges. The sirolimus pharmacokinetic models insufficiently describe sirolimus distribution to relevant physiological compartments. Despite multiple publications describing sirolimus effects on Tcons and Tregs in preclinical and human ex vivo models, consistent parameters relating sirolimus concentrations to circulating Tcons and Tregs could not be found. Each aspect presents a challenge in building a QSP model of sirolimus and its temporal effects on T-cell subsets and GVHD prevention. To optimize GVHD prevention regimens, phase I studies and systematic studies of immunosuppressant concentration-effect association are needed for QSP modeling.

Published
2024

5. Concepts and Applications of Information Theory to Immuno-Oncology

Author

Karolak, Aleksandra, Branciamore, Sergio, McCune, Jeannine S, Lee, Peter P, Rodin, Andrei S, and Rockne, Russell C

Subjects
Biomedical and Clinical Sciences, Immunology, Cancer, Inflammatory and immune system, Allergy and Immunology, Animals, Humans, Information Theory, Medical Oncology, Neoplasms, Signal Transduction, channel capacity, cytokines, entropy, immune signaling, immuno-oncology, information theory, Oncology and Carcinogenesis, Oncology and carcinogenesis
Abstract

Recent successes of immune-modulating therapies for cancer have stimulated research on information flow within the immune system and, in turn, clinical applications of concepts from information theory. Through information theory, one can describe and formalize, in a mathematically rigorous fashion, the function of interconnected components of the immune system in health and disease. Specifically, using concepts including entropy, mutual information, and channel capacity, one can quantify the storage, transmission, encoding, and flow of information within and between cellular components of the immune system on multiple temporal and spatial scales. To understand, at the quantitative level, immune signaling function and dysfunction in cancer, we present a methodology-oriented review of information-theoretic treatment of biochemical signal transduction and transmission coupled with mathematical modeling.

Published
2021

6. Pancreatic Ductal Adenocarcinoma (PDAC): A Review of Recent Advancements Enabled by Artificial Intelligence.

Author

Mukund, Ashwin, Afridi, Muhammad Ali, Karolak, Aleksandra, Park, Margaret A., Permuth, Jennifer B., and Rasool, Ghulam

Subjects
ADENOCARCINOMA, PUBLIC health surveillance, MEDICAL technology, MEDICAL quality control, RESEARCH funding, ARTIFICIAL intelligence, CANCER patient medical care, EARLY detection of cancer, TREATMENT effectiveness, PANCREATIC tumors, METASTASIS, MACHINE learning, DELAYED diagnosis, EVALUATION
Abstract

Simple Summary: Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the deadliest forms of cancer, characterized by high rates of metastasis, late detection, and poor prognoses. Artificial intelligence and machine learning (AI/ML) have proven to be highly effective in improving the current standard of care for many cancers, including PDAC. This review article provides a holistic overview of high-impact, transformative AI/ML applications in various areas of PDAC care. Reflecting a patient's medical journey, these areas include screening, diagnosis, treatment, and post-treatment surveillance. Obstacles and limitations in AI/ML applications within the context of PDAC are also discussed, along with potential solutions and future directions. Collectively, this review article offers novel approaches and meaningful insights, potentially leading to solutions for the multifaceted challenges inherent in PDAC. Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) and machine learning (ML) are emerging as pivotal tools in revolutionizing PDAC care across various dimensions. Consequently, many studies have focused on using AI to improve the standard of PDAC care. This review article attempts to consolidate the literature from the past five years to identify high-impact, novel, and meaningful studies focusing on their transformative potential in PDAC management. Our analysis spans a broad spectrum of applications, including but not limited to patient risk stratification, early detection, and prediction of treatment outcomes, thereby highlighting AI's potential role in enhancing the quality and precision of PDAC care. By categorizing the literature into discrete sections reflective of a patient's journey from screening and diagnosis through treatment and survivorship, this review offers a comprehensive examination of AI-driven methodologies in addressing the multifaceted challenges of PDAC. Each study is summarized by explaining the dataset, ML model, evaluation metrics, and impact the study has on improving PDAC-related outcomes. We also discuss prevailing obstacles and limitations inherent in the application of AI within the PDAC context, offering insightful perspectives on potential future directions and innovations. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Microsensors in the retention treatment of orthodontic patients - literature review

Author

JASIŃSKA, Joanna, ŁAZICKA, Patrycja, JAKUBOWSKA, Eliza, MIZINIAK, Marta, and KAROLAK, Aleksandra

Abstract

JASIŃSKA, Joanna, ŁAZICKA, Patrycja, JAKUBOWSKA, Eliza, MIZINIAK, Marta & KAROLAK, Aleksandra. Microsensors in the retention treatment of orthodontic patients - literature review. Journal of Education, Health and Sport. 2023;41(1):25-34.eISSN 2391-8306. DOIhttp://dx.doi.org/10.12775/JEHS.2023.41.01.002 https://apcz.umk.pl/JEHS/article/view/44012 https://zenodo.org/record/8054006 The journal has had 40 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 21, 2021. No. 32343. Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences). Punkty Ministerialne z 2019 - aktualny rok 40 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 21 grudnia 2021 r. Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159. Przypisane dyscypliny naukowe: Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu); Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu). © The Authors 2023; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 16.05.2023. Revised: 15.06.2023. Accepted: 18.06.2023. Published: 21.06.2023. Microsensors in the retention treatment of orthodontic patients - literature review Mikrosensory w leczeniu retencyjnym pacjentów ortodontycznych – przegląd piśmiennictwa Joanna Jasińska Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu ORCID 0009-0006-3052-902X https://orcid.org/0009-0006-3052-902X E-mail:joannajasinska88@gmail.com Patrycja Łazicka Warszawski Uniwersytet Medyczny ORCID 0009-0000-9018-8155 https://orcid.org/0009-0000-9018-8155 E-mail:pati.lazicka@gmail.com Eliza Jakubowska Studenckie Koło Naukowe Ortopedii Szczękowej i Ortodoncji, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu ORCID 0009-0007-7372-5327 https://orcid.org/0009-0007-7372-5327 E-mail:eliza.jakubowska13@gmail.com Marta Miziniak Uniwersytet Medyczny w Białymstoku https://orcid.org/0009-0001-9626-3432 E-mail:miziniak.marta@gmail.com Aleksandra Karolak Uniwersytet Medyczny w Białymstoku ORCID 0009-0007-1179-1126 https://orcid.org/0009-0007-1179-1126 E-mail:aleksandrakarolak02@gmail.com ABSTRACT Introduction Removable retainers have been successfully used for many years as an independent or additional form of retention in patients after orthodontic treatment. Unfortunately, it has been proven that most patients do not follow the orthodontist's recommendations and do not use the braces for the number of hours necessary to stabilize the treatment effects. It has therefore become necessary to look for solutions and devices that are able to objectively record the actual time of retainers use. Aim of the study The aim of the study was to assess the usefulness of electronic microsensors in monitoring wear time of removable retainers. Materials and methods A search was conducted using PubMed, Google Scholar, ResearchGate databases. Articles were searched in English using the following key words: “microsensors”, “retention”, “orthodontic”, “TheraMon”, “Smart Retainer”. Results The results of the literature review show that microsensors embedded in the elements of removable retainers are a valuable tool for monitoring the time of their use. Awareness of the presence of electronic sensors increases patient discipline. In addition, they provide data that, apart from objectively documenting the course of retention treatment, may be used in the future to determine optimal retention protocols. Conclusions The retention stage is an indispensable element of orthodontic treatment. The use of microsensors built into removable retainers can help to improve the stability of treatment results. However, further research and work are needed to improve the performance and reliability of this type of electronic sensors. Key words:microsensors, retention, orthodontics, TheraMon, Smart Retainer ABSTRAKT Wprowadzenie Zdejmowane aparaty retencyjne są z powodzeniem stosowane od wielu lat jako samodzielna lub dodatkowa forma retencji u pacjentów po leczeniu ortodontycznym. Niestety udowodniono, że większość pacjentów nie stosuje się do zaleceń ortodonty i nie korzysta z aparatu przez liczbę godzin niezbędną do ustabilizowania efektów leczenia. Konieczne stało się zatem poszukiwanie rozwiązań i urządzeń, który są w stanie obiektywnie rejestrować rzeczywisty czas użytkowania retainerów. Cel pracy Celem pracy była ocena użyteczności elektronicznych mikrosensorów w monitorowaniu czasu użytkowania zdejmowanych aparatów retencyjnych. Materiały i metodyka Przeanalizowano bazy danych PubMed, Google Scholar, ResearchGate. Artykuły wyszukiwano w języku angielskim z wykorzystaniem następujących słów kluczy: „mikrosensory”, „retencja”, „ortodoncja”, „TheraMon”, „Smart Retainer”. Wyniki Wynikiprzeglądupiśmiennictwapozwalająstwierdzić,żemikrosensory umieszczane w elementach zdejmowanych aparatów retencyjnych stanowią wartościowe narzędzie służące do monitorowania czasu ich użytkowania. Świadomość obecności czujników elektronicznych zwiększa dyscyplinę pacjentów. Ponadto dostarczają dane, które poza obiektywnym dokumentowaniem przebiegu leczenia retencyjnego mogą posłużyć w przyszłości do ustalenia optymalnych protokołów retencji. Podsumowanie Etap retencji jest nieodzownym elementem leczenia ortodontycznego. Użycie mikrosensorów wbudowanych w zdejmowane aparaty retencyjne może przyczynić się do poprawy stabilności wyników leczenia. Konieczne są jednak dalsze badania oraz prace celem ulepszenia działania oraz poprawy niezawodności tego typu urządzeń. Słowa klucze: mikrosensory, retencja, ortodoncja, TheraMon, Smart Retainer

Published
2023

19. Multi-omics approach to identifying isoform variants as therapeutic targets in cancer patients

Author

Shaw, Timothy I., Zhao, Bi, Li, Yuxin, Wang, Hong, Wang, Liang, Manley, Brandon, Stewart, Paul A., and Karolak, Aleksandra

Subjects
Cancer Research, Oncology
Abstract

Cancer-specific alternatively spliced events (ASE) play a role in cancer pathogenesis and can be targeted by immunotherapy, oligonucleotide therapy, and small molecule inhibition. However, identifying actionable ASE targets remains challenging due to the uncertainty of its protein product, structure impact, and proteoform (protein isoform) function. Here we argue that an integrated multi-omics profiling strategy can overcome these challenges, allowing us to mine this untapped source of targets for therapeutic development. In this review, we will provide an overview of current multi-omics strategies in characterizing ASEs by utilizing the transcriptome, proteome, and state-of-art algorithms for protein structure prediction. We will discuss limitations and knowledge gaps associated with each technology and informatics analytics. Finally, we will discuss future directions that will enable the full integration of multi-omics data for ASE target discovery.

Published
2022

27. Collagen Production and Niche Engineering: A Novel Strategy for Cancer Cells to Survive Acidosis and Evolve

Author

Damaghi, Mehdi, primary, Byrne, Samantha, additional, Xu, Liping, additional, Tafreshi, Narges, additional, Fang, Bin, additional, Koomen, John M., additional, Karolak, Aleksandra, additional, Chen, Tingan, additional, Johnson, Joseph, additional, Gallant, Nathan D., additional, Marusyk, Andriy, additional, and Gillies, Robert J., additional

Published
2019
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39. Enhancing synergy of CAR T cell therapy and oncolytic virus therapy for pancreatic cancer

Author

Walker, Rachel, primary, Navas, Pedro E., additional, Friedman, Samuel H., additional, Galliani, Simona, additional, Karolak, Aleksandra, additional, Macfarlane, Fiona, additional, Noble, Robert, additional, Poleszczuk, Jan, additional, Russell, Shonagh, additional, Rejniak, Katarzyna A., additional, Shahmoradi, Amir, additional, Ziebell, Frederik, additional, Brayer, Jason, additional, Abate-Daga, Daniel, additional, and Enderling, Heiko, additional

Published
2016
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49. Using Photoacoustic Calorimetry to Study the cis- to trans- Photoisomerization of the [Ru(II)(2,2’-bipyridine)2(H2O)2]2+ Complex in Aqueous Solution.

Author

Word, Tarah A., Karolak, Aleksandra, Cioce, Christian R., Van Der Vaart, Arjan, and Larsen, Randy W.

Subjects
*CALORIMETRY, *PHOTOISOMERIZATION, *RUTHENIUM compounds, *PHOTOACOUSTIC effect, *DENSITY functional theory, *ISOMERIZATION, *PHOTOLYSIS (Chemistry)
Abstract

The mechanism associated with the cis- to trans-photoisomerization of Ru(II)(2,2’-bipyridine)2(H2O)2 ([Ru(bpy)2(H2O)2]2+) complex in water has been examined using photoacoustic calorimetry (PAC) and density functional theory (DFT). Photolysis of the cis-[Ru(bpy)2(H2O)2]2+ complex results in a ΔH of -27 ±5 kcal mol–1 and ΔV of 0.1±2 mL mol–1. The DFT calculations give a ΔEcis-trans of +12 kcal mol–1, indicating that the observed ΔH contains significant contributions from changes in solvation. The DFT analysis of putative intermediates [Ru(bpy)2(H2O)]2+ and [Ru(bpy)2(H2O)3]2+ suggests the possibility of an associative mechanism for the isomerization process. [ABSTRACT FROM AUTHOR]

Published
2016
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50. Molecular Dynamics Simulations of 5-Hydroxycytosine Damaged DNA.

Author

Karolak, Aleksandra and van der Vaart, Arjan

Subjects
*MOLECULAR dynamics, *CYTOSINE, *DNA damage, *ADENINE, *FLEXIBILITY (Mechanics)
Abstract

Oxidation of cytosine is a leading cause of mutations and can lead to cancer. Here we report molecular dynamics simulations that characterized the structure and flexibility of 5-hydroxycytosine damaged DNA. A total of four systems were studied: undamaged DNA, damaged DNA base paired to a matching guanine, damaged DNA base paired to a mismatching adenine, and the corresponding undamaged mismatched strand. The simulations showed high spatial similarity between undamaged and damaged DNA; however, the matched damaged strand had greater overtwisting flexibility, and for both the matched and unmatched strands sugar puckering was much more flexible at the damaged site. The mismatch introduced larger changes, notably a loss in hydrogen bonding and a gain in stacking interactions, as well as effects on base pair and step geometry and solvation. Implications for damage recognition are discussed. [ABSTRACT FROM AUTHOR]

Published
2016
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