Artificial intelligence in medicine: A comprehensive survey of medical doctor's perspectives in Portugal.

Artificial Intelligence (AI) is increasingly influential across various sectors, including healthcare, with the potential to revolutionize clinical practice. However, risks associated with AI adoption in medicine have also been identified. Despite the general understanding that AI will impact healthcare, studies that assess the perceptions of medical doctors about AI use in medicine are still scarce. We set out to survey the medical doctors licensed to practice medicine in Portugal about the impact, advantages, and disadvantages of AI adoption in clinical practice. We designed an observational, descriptive, cross-sectional study with a quantitative approach and developed an online survey which addressed the following aspects: impact on healthcare quality of the extraction and processing of health data via AI; delegation of clinical procedures on AI tools; perception of the impact of AI in clinical practice; perceived advantages of using AI in clinical practice; perceived disadvantages of using AI in clinical practice and predisposition to adopt AI in professional activity. Our sample was also subject to demographic, professional and digital use and proficiency characterization. We obtained 1013 valid, fully answered questionnaires (sample representativeness of 99%, confidence level (p< 0.01), for the total universe of medical doctors licensed to practice in Portugal). Our results reveal that, in general terms, the medical community surveyed is optimistic about AI use in medicine and are predisposed to adopt it while still aware of some disadvantages and challenges to AI use in healthcare. Most medical doctors surveyed are also convinced that AI should be part of medical formation. These findings contribute to facilitating the professional integration of AI in medical practice in Portugal, aiding the seamless integration of AI into clinical workflows by leveraging its perceived strengths according to healthcare professionals. This study identifies challenges such as gaps in medical curricula, which hinder the adoption of AI applications due to inadequate digital health training. Due to high professional integration in the healthcare sector, particularly within the European Union, our results are also relevant for other jurisdictions and across diverse healthcare systems.

Facilitators of and Barriers to Accessing Hospital Medical Specialty Telemedicine Consultations During the COVID-19 Pandemic: Systematic Review.

BACKGROUND: The COVID-19 pandemic accelerated the digital transition in health care, which required a rapid adaptation for stakeholders. Telemedicine has emerged as an ideal tool to ensure continuity of care by allowing remote access to specialized medical services. However, its rapid implementation has exacerbated disparities in health care access, especially for the most susceptible populations. OBJECTIVE: We aimed to characterize the determinant factors (facilitators and barriers) of access to hospital medical specialty telemedicine consultations during the COVID-19 pandemic and to identify the main opportunities and challenges (technological, ethical, legal, and social) generated by the use of telemedicine in the context of the COVID-19 pandemic. METHODS: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 4 databases (Scopus, Web of Science, PubMed, and Cochrane COVID-19 Study Register) were searched for empirical studies published between January 3, 2020, and December 31, 2021, using established criteria. The protocol of this review was registered and published in PROSPERO (CRD42022302825). A methodological quality assessment was performed, and the results were integrated into a thematic synthesis. The identification of the main opportunities and challenges was done by interpreting and aggregating the thematic synthesis results. RESULTS: Of the 106 studies identified, 9 met the inclusion criteria and the intended quality characteristics. All studies were originally from the United States. The following facilitating factors of telemedicine use were identified: health insurance coverage; prevention of SARS-CoV-2 infection; access to internet services; access to technological devices; better management of work-life balance; and savings in travel costs. We identified the following barriers to telemedicine use: lack of access to internet services; lack of access to technological devices; racial and ethnic disparities; low digital literacy; low income; age; language barriers; health insurance coverage; concerns about data privacy and confidentiality; geographic disparities; and the need for complementary diagnostic tests or the delivery of test results. CONCLUSIONS: The facilitating factors and barriers identified in this systematic review present different opportunities and challenges, including those of a technological nature (access to technological devices and internet services and level of digital literacy), a sociocultural and demographic nature (ethnic and racial disparities, geographic disparities, language barriers, and age), a socioeconomic nature (income level and health insurance coverage), and an ethical and legal nature (data privacy and confidentiality). To expand telemedicine access to hospital-based specialty medical consultations and provide high-quality care to all, including the most susceptible communities, the challenges identified must be thoroughly researched and addressed with informed and dedicated responses.

LOCUS (LOng Covid-Understanding Symptoms, events and use of services in Portugal): A three-component study protocol.

Approximately 10% of patients experience symptoms of Post COVID-19 Condition (PCC) after a SARS-CoV-2 infection. Akin acute COVID-19, PCC may impact a multitude of organs and systems, such as the cardiovascular, respiratory, musculoskeletal, and neurological systems. The frequency and associated risk factors of PCC are still unclear among both community and hospital settings in individuals with a history of COVID-19. The LOCUS study was designed to clarify the PCC's burden and associated risk factors. LOCUS is a multi-component study that encompasses three complementary building blocks. The "Cardiovascular and respiratory events following COVID-19" component is set to estimate the incidence of cardiovascular and respiratory events after COVID-19 in eight Portuguese hospitals via electronic health records consultation. The "Physical and mental symptoms following COVID-19" component aims to address the community prevalence of self-reported PCC symptoms through a questionnaire-based approach. Finally, the "Treating and living with Post COVID-19 Condition" component will employ semi-structured interviews and focus groups to characterise reported experiences of using or working in healthcare and community services for the treatment of PCC symptoms. This multi-component study represents an innovative approach to exploring the health consequences of PCC. Its results are expected to provide a key contribution to the optimisation of healthcare services design.

Biobanks for aging research - perceptions and choices among rheumatology outpatients.

OBJECTIVE: Biobanks for research (BBR) have enormous value for research, including those specifically oriented to chronic diseases. Knowing public attitudes and perceptions is key to design and implement patient-centered BBR. We assessed patient awareness, perception and choices among rheumatology outpatients regarding aging biobanking activities. METHODS: We conducted a cross-sectional survey of patients, aged 50 or older, attending an outpatient rheumatology tertiary department. Demographic data and perceptions about biobanking were collected and statistical analysis was performed. RESULTS: 132 valid questionnaires were obtained (mean age: 63,4; 68,2% female; mean education years: 8,35). 61,7% of respondents did not know the specific term "biobank", 57,7% knew they could donate biological material for BBR, 89,9% agreed with these infrastructures and 88,3% would consider participation Those participants with more years of education were more knowledgeable and prone to biobank participation. Willingness to participate in BBR was mainly related (86,4%) to the advancement of scientific knowledge and not individual gain. Scientific research institutes were indicated as the most adequate institutions to manage BBR. Informed consent, anonymity and confidentiality ranked as top requisites for biobank participation. 61,3% of respondents expressed their agreement with aging biobanks, considering these as a sign of respect for specific problems of people of older ages such as higher disease burdens. CONCLUSION: Knowledge of biobanks was found to be limited. Participants were positive toward the setting up of biobanks in general and patient-centered aging biobanks in particular. Knowledge about biobanks and acceptance were higher among participants with higher education years.

Digital Technologies and Data Science as Health Enablers: An Outline of Appealing Promises and Compelling Ethical, Legal, and Social Challenges.

Digital technologies and data science have laid down the promise to revolutionize healthcare by transforming the way health and disease are analyzed and managed in the future. Digital health applications in healthcare include telemedicine, electronic health records, wearable, implantable, injectable and ingestible digital medical devices, health mobile apps as well as the application of artificial intelligence and machine learning algorithms to medical and public health prognosis and decision-making. As is often the case with technological advancement, progress in digital health raises compelling ethical, legal, and social implications (ELSI). This article aims to succinctly map relevant ELSI of the digital health field. The issues of patient autonomy; assessment, value attribution, and validation of health innovation; equity and trustworthiness in healthcare; professional roles and skills and data protection and security are highlighted against the backdrop of the risks of dehumanization of care, the limitations of machine learning-based decision-making and, ultimately, the future contours of human interaction in medicine and public health. The running theme to this article is the underlying tension between the promises of digital health and its many challenges, which is heightened by the contrasting pace of scientific progress and the timed responses provided by law and ethics. Digital applications can prove to be valuable allies for human skills in medicine and public health. Similarly, ethics and the law can be interpreted and perceived as more than obstacles, but also promoters of fairness, inclusiveness, creativity and innovation in health.

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.

RhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding.

Epithelial wound healing relies on tissue movements and cell shape changes. Our work shows that, immediately after wounding, there was a dramatic cytoskeleton remodeling consisting of a pulse of actomyosin filaments that assembled in cells around the wound edge and flowed from cell to cell toward the margin of the wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and that it elicited a wave of apical cell constriction that culminated in the formation of the leading edge actomyosin cable, a structure that is essential for wound closure. Calcium signaling played an important role in this process, as its intracellular concentration increased dramatically immediately after wounding, and down-regulation of transient receptor potential channel M, a stress-activated calcium channel, also impaired the actomyosin flow. Lowering the activity of Gelsolin, a known calcium-activated actin filament-severing protein, also impaired the wound response, indicating that cleaving the existing actin filament network is an important part of the cytoskeleton remodeling process.

The role of transcription-independent damage signals in the initiation of epithelial wound healing.

Wound healing is an essential biological process that comprises sequential steps aimed at restoring the architecture and function of damaged cells and tissues. This process begins with conserved damage signals, such as Ca2+, hydrogen peroxide (H2O2) and ATP, that diffuse through epithelial tissues and initiate immediate gene transcription-independent cellular effects, including cell shape changes, the formation of functional actomyosin structures and the recruitment of immune cells. These events integrate the ensuing transcription of specific wound response genes that further advance the wound healing response. The immediate importance of transcription-independent damage signals illustrates that healing a wound begins as soon as damage occurs.

The role of transcription-independent damage signals in the initiation of epithelial wound healing.

Wound healing is an essential biological process that comprises sequential steps aimed at restoring the architecture and function of damaged cells and tissues. This process begins with conserved damage signals, such as Ca(2+), hydrogen peroxide (H2O2) and ATP, that diffuse through epithelial tissues and initiate immediate gene transcription-independent cellular effects, including cell shape changes, the formation of functional actomyosin structures and the recruitment of immune cells. These events integrate the ensuing transcription of specific wound response genes that further advance the wound healing response. The immediate importance of transcription-independent damage signals illustrates that healing a wound begins as soon as damage occurs.

F11-mediated inhibition of RhoA signalling enhances the spread of vaccinia virus in vitro and in vivo in an intranasal mouse model of infection.

The cortical actin cytoskeleton beneath the plasma membrane represents a physical barrier that vaccinia virus has to overcome during its exit from an infected cell. Previous observations using overexpression and pharmacological approaches suggest that vaccinia enhances its release by modulating the cortical actin cytoskeleton by inhibiting RhoA signalling using the viral protein F11. We have now examined the role of F11 and its ability to interact with RhoA to inhibit its downstream signalling in the spread of vaccinia infection both in vitro and in vivo. Live cell imaging over 48 hours reveals that loss of F11 or its ability to bind RhoA dramatically reduces the rate of cell-to-cell spread of the virus in a cell monolayer. Cells infected with the DeltaF11L virus also maintained their cell-to-cell contacts, and did not undergo virus-induced motility as observed during wild-type infections. The DeltaF11L virus is also attenuated in intranasal mouse models of infection, as it is impaired in its ability to spread from the initial sites of infection to the lungs and spleen. Loss of the ability of F11 to bind RhoA also reduces viral spread in vivo. Our results clearly establish that viral-mediated inhibition of RhoA signalling can enhance the spread of infection not only in cell monolayers, but also in vivo.

Engagement of Toll-like receptor 2 in mouse macrophages infected with Mycobacterium avium induces non-oxidative and TNF-independent anti-mycobacterial activity.

Toll-like receptor (TLR) 2 plays an important role in the immune response to mycobacterial infections, being required for optimal immunity against certain virulent Mycobacterium avium strains. Here we analyzed the role of TLR2 in the intra-macrophagic growth of M. avium, using macrophages from TLR2-deficient mice. We found that the engagement of TLR2/TLR6 and/or TLR2/TLR1 receptors induced bacteriostasis of M. avium inside bone marrow-derived macrophages in a MyD88-dependent way. Additionally, lipoproteins from the cell envelope of M. avium with a molecular mass of 20-25 kDa triggered this TLR2 pathway, leading to a decrease in the growth of the mycobacteria. Although TLR2 engagement induced the production of TNF, this cytokine as well as nitric oxide and superoxide molecules were not necessary for TLR2-mediated bacteriostasis. Finally, TLR ligation did not induce the expression of the 47-kDa guanosine triphosphatase (LRG-47) but it promoted an increased maturation of the phagosome with regards to acquisition of LAMP1. Our data show that triggering TLR2 inhibited M. avium growth by an as-yet-unknown mechanism that may involve increased phagosome maturation.

F11L-mediated inhibition of RhoA-mDia signaling stimulates microtubule dynamics during vaccinia virus infection.

Microtubules play an important role in the transport of viral pathogens during the establishment of their infection cycles. The microtubule cytoskeleton also facilitates efficient release of newly assembled progeny at later stages of infection. However, the precise effects of viral infection on microtubule dynamics are not understood. Using live-cell imaging, we show that vaccinia virus stimulates increases in peripheral microtubule dynamics at 8 hr postinfection. Infection also increases the frequency with which microtubule tips reach the cell cortex and reduces the acetylation of peripheral microtubules consistent with their increased dynamics. These virus-induced changes in peripheral microtubule dynamics are independent of the GTPases Rac and Cdc42, which are known stimulators of microtubule dynamics in uninfected cells. They do, however, require F11L-mediated inhibition of signaling via the GTPase RhoA and its effector, mDia. We suggest that increases in peripheral microtubule dynamics and cortical targeting contribute to enhanced virus release.

The release of vaccinia virus from infected cells requires RhoA-mDia modulation of cortical actin.

Prior to being released from the infected cell, intracellular enveloped vaccinia virus particles are transported from their perinuclear assembly site to the plasma membrane along microtubules by the motor kinesin-1. After fusion with the plasma membrane, stimulation of actin tails beneath extracellular virus particles acts to enhance cell-to-cell virus spread. However, we lack molecular understanding of events that occur at the cell periphery just before and during the liberation of virus particles. Using live cell imaging, we show that virus particles move in the cell cortex, independently of actin tail formation. These cortical movements and the subsequent release of virus particles, which are both actin dependent, require F11L-mediated inhibition of RhoA-mDia signaling. We suggest that the exit of vaccinia virus from infected cells has strong parallels to exocytosis, as it is dependent on the assembly and organization of actin in the cell cortex.

Vaccinia virus-induced cell motility requires F11L-mediated inhibition of RhoA signaling.

RhoA signaling plays a critical role in many cellular processes, including cell migration. Here we show that the vaccinia F11L protein interacts directly with RhoA, inhibiting its signaling by blocking the interaction with its downstream effectors Rho-associated kinase (ROCK) and mDia. RNA interference-mediated depletion of F11L during infection resulted in an absence of vaccinia-induced cell motility and inhibition of viral morphogenesis. Disruption of the RhoA binding site in F11L, which resembles that of ROCK, led to an identical phenotype. Thus, inhibition of RhoA signaling is required for both vaccinia morphogenesis and virus-induced cell motility.

HFE cross-talks with the MHC class I antigen presentation pathway.

HFE is a protein known to be involved in iron metabolism; yet, other than its homology with major histocompatibility complex (MHC) class I molecules, it has not been described as having an immunologic function. Here we report that peripheral blood mononuclear cells (PBMCs) from patients with hereditary hemochromatosis (HH) carrying the C282Y mutation in HFE have reduced cell-surface expression of MHC class I due to an enhanced endocytosis rate of MHC class I molecules caused by premature peptide and beta2-microglobulin dissociation. This faster turnover also leads to increased expression levels of cell-surface free class I heavy chains in mutant PBMCs. Biochemical analysis indicates an earlier peptide loading and endoplasmic reticulum maturation of MHC class I molecules in C282Y mutant cells. Thermostability assays further showed that in HFE mutants the MHC class I peptide loading gives rise to low-stability heterotrimers that dissociate prematurely during its intracellular traffic. The present results suggest the existence of an intriguing cross-talk between a particular HFE mutation and the classical MHC class I route. These findings constitute the first description of peptide presentation pathway abnormalities linked to HFE and provide additional evidence for the occurrence of immunologic defects in patients with HH.

Limited role of the Toll-like receptor-2 in resistance to Mycobacterium avium.

The role of the Toll-like receptor (TLR)-2 in the generation of protective immunity to Mycobacterium avium was evaluated using gene-disrupted mice. TLR-2-/- mice were more susceptible than wild-type C57Bl/6 mice to M. avium strains that were able to proliferate in vivo before the development of protective immunity and mycobacteriostasis. In contrast, the elimination of non-virulent strains was not affected by the mutation. The generation of interferon-gamma (IFN-gamma)-producing T cells and the expression of the interleukin-12 p40 gene were reduced in TLR-2-deficient mice as compared to C57Bl/6 mice early during infection with M. avium strain 2447. The generation of protective CD4+ T cells was also compromised in the mutated mice as compared with the controls. Our data show that TLR-2 is required for optimal immunity against certain virulent M. avium strains.