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Book ; Online ; E-Book: Medicine Without Meds

Ho, Dean / Sapanel, Yoann / Blasiak, Agata

Transforming Patient Care with Digital Therapies

2023

Abstract: Digital therapeutics (DTx) is a dynamic, emerging subcategory within the larger supercategory field of 'digital health' or 'digital medicine'. As defined by the nonprofit trade group, Digital Therapeutics Alliance, "DTx deliver clinical-grade ... ...

Author's details	edited by Dean Ho, Yoann Sapanel, and Agata Blasiak
Abstract	"Digital therapeutics (DTx) is a dynamic, emerging subcategory within the larger supercategory field of 'digital health' or 'digital medicine'. As defined by the nonprofit trade group, Digital Therapeutics Alliance, "DTx deliver clinical-grade therapeutic interventions to patients [that] may be used independently or in tandem with in-person or remote clinician-delivered therapy to optimize patient outcomes." In this new book, three expert editors have enlisted the support of contributors to explain what DTx represents (and how it differs from other digital health solutions), how DTX solutions can help individuals and their healthcare providers meet their health goals, and how DTx tools can be conceptualized, created, and brought to market"--
Keywords	Therapeutics
Subject code	621
Language	English
Size	1 online resource (332 pages)
Edition	First edition.
Publisher	Johns Hopkins University Press
Publishing place	Baltimore, Maryland
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	1-4214-4704-5 ; 978-1-4214-4704-9
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: G Protein-Coupled Receptor Dimerization-What Next?

Dziedzicka-Wasylewska, Marta / Polit, Agnieszka / Błasiak, Ewa / Faron-Górecka, Agata

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Numerous studies highlight the therapeutic potential of G protein-coupled receptor (GPCR) heterodimers, emphasizing their significance in various pathological contexts. Despite extensive basic research and promising outcomes in animal models, the ... ...

Abstract	Numerous studies highlight the therapeutic potential of G protein-coupled receptor (GPCR) heterodimers, emphasizing their significance in various pathological contexts. Despite extensive basic research and promising outcomes in animal models, the translation of GPCR heterodimer-targeting drugs into clinical use remains limited. The complexities of in vivo conditions, particularly within thecomplex central nervous system, pose challenges in fully replicating physiological environments, hindering clinical success. This review discusses examples of the most studied heterodimers, their involvement in nervous system pathology, and the available data on their potential ligands. In addition, this review highlights the intricate interplay between lipids and GPCRs as a potential key factor in understanding the complexity of cell signaling. The multifaceted role of lipids in modulating the dynamics of GPCR dimerization is explored, shedding light on the elaborate molecular mechanisms governing these interactions.
MeSH term(s)	Animals ; Dimerization ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Cell Membrane/metabolism ; Lipids
Chemical Substances	Receptors, G-Protein-Coupled ; Lipids
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063089
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Article ; Online: Effect of Vitamin D

Pich, Karolina / Rajewska, Jesika / Kamińska, Kinga / Tchurzyk, Marcelina / Szlaga, Agata / Sambak, Patryk / Błasiak, Anna / Grzesiak, Małgorzata / Rak, Agnieszka

Cells

2023 Volume 12, Issue 16

Abstract: Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder with disrupted uterus structure and function. A positive effect of vitamin D: Methods: We analyzed the plasma levels and uterine transcript and protein expression of RARRES2 and ... ...

Abstract	Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder with disrupted uterus structure and function. A positive effect of vitamin D Methods: We analyzed the plasma levels and uterine transcript and protein expression of RARRES2 and ADIPOQ and their receptors (CCRL2, CMKLR1, GPR1, and ADIPOR1 and ADIPOR2, respectively) in rats with letrozole-induced PCOS. Results: In control animals, VD Conclusions: our findings indicate a new mechanism of VD
MeSH term(s)	Female ; Animals ; Rats ; Humans ; Adiponectin ; Polycystic Ovary Syndrome ; Cholecalciferol/pharmacology ; Uterus ; Adipokines
Chemical Substances	Adiponectin ; Cholecalciferol (1C6V77QF41) ; Adipokines
Language	English
Publishing date	2023-08-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12162026
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Article ; Online: Bidirectional Communication between the Pontine Nucleus Incertus and the Medial Septum Is Carried Out by Electrophysiologically-Distinct Neuronal Populations.

Trenk, Aleksandra / Walczak, Magdalena / Szlaga, Agata / Pradel, Kamil / Blasiak, Anna / Blasiak, Tomasz

The Journal of neuroscience : the official journal of the Society for Neuroscience

2022 Volume 42, Issue 11, Page(s) 2234–2252

Abstract: Theta oscillations are key brain rhythm involved in memory formation, sensorimotor integration, and control of locomotion and behavioral states. Generation and spatiotemporal synchronization of theta oscillations rely on interactions between brain nuclei ...

Abstract	Theta oscillations are key brain rhythm involved in memory formation, sensorimotor integration, and control of locomotion and behavioral states. Generation and spatiotemporal synchronization of theta oscillations rely on interactions between brain nuclei forming a large neural network, which includes pontine nucleus incertus (NI). Here we identified distinct populations of NI neurons, based on the relationship of their firing to hippocampal waves, with a special focus on theta oscillations, and the direction and type of interaction with the medial septum (MS) in male, urethane-anesthetized rats. By recording NI neuronal firing and hippocampal LFP, we described NI neurons that fire action potentials in a theta phase-independent or theta phase-locked and delta wave-independent or delta wave-locked manner. Among hippocampal activity-independent NI neurons, irregular, slow-firing, and regular, fast-firing cells were observed, while hippocampal oscillation-/wave-locked NI neurons were of a bursting or nonbursting type. By projection-specific optotagging, we revealed that only fast-firing theta phase-independent NI neurons innervate the MS, rarely receiving feedback information. In contrast, the majority of theta-bursting NI neurons were inhibited by MS stimulation, and this effect was mediated by direct GABAergic input. Described NI neuronal populations differ in reciprocal connections with the septohippocampal system, plausibly forming separate neuronal loops. Our results suggest that theta phase-independent NI neurons participate in theta rhythm generation through direct innervation of the MS, while theta-bursting NI neurons further transmit the rhythmic signal received from the MS to stabilize and/or strengthen rhythmic activity in other structures.
MeSH term(s)	Action Potentials/physiology ; Animals ; Hippocampus/physiology ; Male ; Neurons/physiology ; Raphe Nuclei ; Rats ; Theta Rhythm
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0230-21.2022
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Article: Involving patients in the process: Development of a constipation patient-reported outcome measure for symptoms and quality of life.

Lee, V Vien / Lau, Ni Yin / Blasiak, Agata / Siah, Kewin Tien Ho / Ho, Dean

Computational and structural biotechnology journal

2023 Volume 22, Page(s) 41–49

Abstract: Objective: Patient-reported outcome measures (PROMs) are useful standardized tools to measure current patient health status and well-being. While there are existing constipation-related PROMs, the majority of PROMs were not developed with adequate ... ...

Abstract	Objective: Patient-reported outcome measures (PROMs) are useful standardized tools to measure current patient health status and well-being. While there are existing constipation-related PROMs, the majority of PROMs were not developed with adequate patient involvement and few examined content validity. Accordingly, the current study aimed to develop a constipation PROM with multiple phases of patient and clinician involvement. Methods: To generate PROM items, 15 patients with chronic constipation (age range =28-79 years, 10 females) underwent a qualitative interview exploring their experiences with chronic constipation. Following that, eight clinical experts completed the content validity index (CVI) ratings of all the items generated to assess content validity. Based on results of the content validity assessment, relevant items were maintained and 12 participants with chronic constipation were re-interviewed to obtain feedback about comprehensibility, comprehensiveness and relevance. Results: Six themes and 25 sub-themes emerged from the qualitative interview, and an initial list of 33 symptom items and 18 quality of life (QoL) items were generated. Based on the CVIs calculated, 11 symptom items and nine QoL items were maintained with the scale-content validity index indicating excellent content validity. Overall, participants indicated the PROM to be relevant, comprehensive and easy to understand however, minor amendments were made to improve the three qualities of interest. Conclusion: The current study developed a constipation PROM that measures both symptom severity and constipation-related QoL, with supporting evidence for relevance, comprehensiveness and comprehensibility. Further prioritization should be given to validating and exploring new digital modalities of PROM administration.
Language	English
Publishing date	2023-09-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2023.09.034
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Article ; Online: Physicians' Perspectives on AI in Clinical Decision Support Systems: Interview Study of the CURATE.AI Personalized Dose Optimization Platform.

Vijayakumar, Smrithi / Lee, V Vien / Leong, Qiao Ying / Hong, Soo Jung / Blasiak, Agata / Ho, Dean

JMIR human factors

2023 Volume 10, Page(s) e48476

Abstract: Background: Physicians play a key role in integrating new clinical technology into care practices through user feedback and growth propositions to developers of the technology. As physicians are stakeholders involved through the technology iteration ... ...

Abstract	Background: Physicians play a key role in integrating new clinical technology into care practices through user feedback and growth propositions to developers of the technology. As physicians are stakeholders involved through the technology iteration process, understanding their roles as users can provide nuanced insights into the workings of these technologies that are being explored. Therefore, understanding physicians' perceptions can be critical toward clinical validation, implementation, and downstream adoption. Given the increasing prevalence of clinical decision support systems (CDSSs), there remains a need to gain an in-depth understanding of physicians' perceptions and expectations toward their downstream implementation. This paper explores physicians' perceptions of integrating CURATE.AI, a novel artificial intelligence (AI)-based and clinical stage personalized dosing CDSSs, into clinical practice. Objective: This study aims to understand physicians' perspectives of integrating CURATE.AI for clinical work and to gather insights on considerations of the implementation of AI-based CDSS tools. Methods: A total of 12 participants completed semistructured interviews examining their knowledge, experience, attitudes, risks, and future course of the personalized combination therapy dosing platform, CURATE.AI. Interviews were audio recorded, transcribed verbatim, and coded manually. The data were thematically analyzed. Results: Overall, 3 broad themes and 9 subthemes were identified through thematic analysis. The themes covered considerations that physicians perceived as significant across various stages of new technology development, including trial, clinical implementation, and mass adoption. Conclusions: The study laid out the various ways physicians interpreted an AI-based personalized dosing CDSS, CURATE.AI, for their clinical practice. The research pointed out that physicians' expectations during the different stages of technology exploration can be nuanced and layered with expectations of implementation that are relevant for technology developers and researchers.
MeSH term(s)	Humans ; Artificial Intelligence ; Decision Support Systems, Clinical ; Physicians ; Attitude of Health Personnel ; Qualitative Research
Language	English
Publishing date	2023-10-30
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2292-9495
ISSN (online)	2292-9495
DOI	10.2196/48476
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Article ; Online: Catecholaminergic innervation and D2-like dopamine receptor-mediated modulation of brainstem nucleus incertus neurons in the rat.

Szlaga, Agata / Sambak, Patryk / Gugula, Anna / Trenk, Aleksandra / Gundlach, Andrew L / Blasiak, Anna

Neuropharmacology

2022 Volume 218, Page(s) 109216

Abstract: Nucleus incertus (NI) is a brainstem structure involved in the control of arousal, stress responses and locomotor activity. It was reported recently that NI neurons express the dopamine type 2 (D2) receptor that belongs to the D2-like receptor (D2R) ... ...

Abstract	Nucleus incertus (NI) is a brainstem structure involved in the control of arousal, stress responses and locomotor activity. It was reported recently that NI neurons express the dopamine type 2 (D2) receptor that belongs to the D2-like receptor (D2R) family, and that D2R activation in the NI decreased locomotor activity. In this study, using multiplex in situ hybridization, we observed that GABAergic and glutamatergic NI neurons express D2 receptor mRNA, and that D2 receptor mRNA-positive neurons belong to partially overlapping relaxin-3- and cholecystokinin-positive NI neuronal populations. Our immunohistochemical and viral-based retrograde tract-tracing studies revealed a dense innervation of the NI area by fibers containing the catecholaminergic biosynthesis enzymes, tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH), and indicated the major sources of the catecholaminergic innervation of the NI as the Darkschewitsch, raphe and hypothalamic A13 nuclei. Furthermore, using whole-cell patch clamp recordings, we demonstrated that D2R activation by quinpirole produced excitatory and inhibitory influences on neuronal activity in the NI, and that both effects were postsynaptic in nature. Moreover, the observed effects were cell-type specific, as type I NI neurons were either excited or inhibited, whereas type II NI neurons were mainly excited by D2R activation. Our results reveal that rat NI receives a strong catecholaminergic innervation and suggest that catecholamines acting within the NI are involved in the control of diverse processes, including locomotor activity, social interaction and nociceptive signaling. Our data also strengthen the hypothesis that the NI acts as a hub integrating arousal-related neuronal information.
MeSH term(s)	Animals ; Dopamine/pharmacology ; Neurons ; RNA, Messenger ; Raphe Nuclei/metabolism ; Rats ; Receptors, Dopamine D2/metabolism
Chemical Substances	RNA, Messenger ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-08-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2022.109216
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Article: Understanding the user: Patients' perception, needs, and concerns of health apps for chronic constipation.

Lee, V Vien / Vijayakumar, Smrithi / Lau, Ni Yin / Blasiak, Agata / Siah, Kewin Tien Ho / Ho, Dean

Digital health

2022 Volume 8, Page(s) 20552076221104673

Abstract: Objective: Chronic constipation is a prevalent gastrointestinal disorder that requires long-term management and treatment adherence. With increasing smartphone usage, health app adoption represents an opportunity to incorporate personalized, patient-led ...

Abstract	Objective: Chronic constipation is a prevalent gastrointestinal disorder that requires long-term management and treatment adherence. With increasing smartphone usage, health app adoption represents an opportunity to incorporate personalized, patient-led care into chronic constipation management. Despite the number of apps available targeting patients with constipation, studies have not yet examined user needs and barriers towards successful app adoption and sustained usage. Accordingly, the current study explored user perception, needs, and concerns of health apps in patients with chronic constipation. Methods: Fifteen participants with chronic constipation (age range = 28-79 years, 10 females) in Singapore completed a 60 min semi-structured qualitative interview exploring participant's experiences with and attitudes towards chronic constipation and health apps. Participants also completed two questionnaires regarding their constipation symptoms and general technology usage. Interviews were audio-recorded, transcribed verbatim, and coded using NVivo. Results: Four themes and 10 sub-themes were identified using inductive thematic analysis. Themes and sub-themes cover importance of patient identity, disease-based expectations of health apps, barriers towards adoption and sustained usage of health apps, necessary conditions when adopting health apps (including perception of supportive benefits, clear understanding of app intention, personalized technology, and trusted sources), and push factor expectations which includes creative engagement and incentivization embedded within the app. Conclusion: The findings captured barriers and key elements necessary for successful health app adoption and continued usage by patients with chronic constipation. Identified elements that matter to patients can provide app developers with user-focused insights and recommendations to develop effective health apps that sustain user engagement.
Language	English
Publishing date	2022-05-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819396-9
ISSN	2055-2076
ISSN	2055-2076
DOI	10.1177/20552076221104673
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Article ; Online: Artificial Intelligence in Clinical Oncology: From Data to Digital Pathology and Treatment.

Senthil Kumar, Kirthika / Miskovic, Vanja / Blasiak, Agata / Sundar, Raghav / Pedrocchi, Alessandra Laura Giulia / Pearson, Alexander T / Prelaj, Arsela / Ho, Dean

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2023 Volume 43, Page(s) e390084

Abstract: Recently, a wide spectrum of artificial intelligence (AI)-based applications in the broader categories of digital pathology, biomarker development, and treatment have been explored. In the domain of digital pathology, these have included novel analytical ...

Abstract	Recently, a wide spectrum of artificial intelligence (AI)-based applications in the broader categories of digital pathology, biomarker development, and treatment have been explored. In the domain of digital pathology, these have included novel analytical strategies for realizing new information derived from standard histology to guide treatment selection and biomarker development to predict treatment selection and response. In therapeutics, these have included AI-driven drug target discovery, drug design and repurposing, combination regimen optimization, modulated dosing, and beyond. Given the continued advances that are emerging, it is important to develop workflows that seamlessly combine the various segments of AI innovation to comprehensively augment the diagnostic and interventional arsenal of the clinical oncology community. To overcome challenges that remain with regard to the ideation, validation, and deployment of AI in clinical oncology, recommendations toward bringing this workflow to fruition are also provided from clinical, engineering, implementation, and health care economics considerations. Ultimately, this work proposes frameworks that can potentially integrate these domains toward the sustainable adoption of practice-changing AI by the clinical oncology community to drive improved patient outcomes.
MeSH term(s)	Humans ; Artificial Intelligence ; Drug Design ; Drug Discovery ; Medical Oncology
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.1200/EDBK_390084
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Article ; Online: CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence.

Blasiak, Agata / Khong, Jeffrey / Kee, Theodore

SLAS technology

2019 Volume 25, Issue 2, Page(s) 95–105

Abstract: The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials' results provide the basis for guidance and support for official protocols that clinicians use to base their ... ...

Abstract	The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials' results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual's response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team's experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach-phenotypic personalized medicine (PPM)-finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals' lives.
MeSH term(s)	Artificial Intelligence ; Dose-Response Relationship, Drug ; Humans ; Phenotype ; Precision Medicine
Language	English
Publishing date	2019-11-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2900310-6
ISSN	2472-6311 ; 2472-6303
ISSN (online)	2472-6311
ISSN	2472-6303
DOI	10.1177/2472630319890316
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