Docking Foundations: From Rigid to Flexible Docking.

Despite the development of methods for the experimental determination of protein structures, the dissonance between the number of known sequences and their solved structures is still enormous. This is particularly evident in protein-protein complexes. To fill this gap, diverse technologies have been developed to study protein-protein interactions (PPIs) in a cellular context including a range of biological and computational methods. The latter derive from techniques originally published and applied almost half a century ago and are based on interdisciplinary knowledge from the nexus of the fields of biology, chemistry, and physics about protein sequences, structures, and their folding. Protein-protein docking, the main protagonist of this chapter, is routinely treated as an integral part of protein research. Herein, we describe the basic foundations of the whole process in general terms, but step by step from protein representations through docking methods and evaluation of complexes to their final validation.

Machine Learning Methods in Protein-Protein Docking.

An exponential increase in the number of publications that address artificial intelligence (AI) usage in life sciences has been noticed in recent years, while new modeling techniques are constantly being reported. The potential of these methods is vast-from understanding fundamental cellular processes to discovering new drugs and breakthrough therapies. Computational studies of protein-protein interactions, crucial for understanding the operation of biological systems, are no exception in this field. However, despite the rapid development of technology and the progress in developing new approaches, many aspects remain challenging to solve, such as predicting conformational changes in proteins, or more "trivial" issues as high-quality data in huge quantities.Therefore, this chapter focuses on a short introduction to various AI approaches to study protein-protein interactions, followed by a description of the most up-to-date algorithms and programs used for this purpose. Yet, given the considerable pace of development in this hot area of computational science, at the time you read this chapter, the development of the algorithms described, or the emergence of new (and better) ones should come as no surprise.

[How much digital public health is in public health degree programs? A systematic analysis of module handbooks in German full-time study programs at public colleges and universities]. / Wie viel Digital Public Health steckt in Public-Health-Studiengängen? Eine systematische Modulhandbuchanalyse von Vollzeitstudiengängen an öffentlichen Hochschulen und Universitäten in Deutschland.

BACKGROUND: Professionals, especially in the field of digital public health (DiPH), are crucial for a successful digital transformation in social and health care. However, it is still unclear to what extent academic professionals are taught DiPH-related content in their public health (PH) studies. METHODS: This study used a systematic module handbook analysis to analyze accredited full-time PH-oriented degree programs at public colleges and universities in Germany for DiPH-related module content. Through the "Hochschulkompass" platform and the member programs of the German Public Health Association (DGPH), 422 programs were identified. Included module handbooks were evaluated by content analysis using MAXQDA. RESULTS: Only 10 bachelor and 6 master programs contain DiPH. They are heterogeneous in their focus and belong to different subfields of public health ("methods, definition, history, and social medicine" = 5; "health management" = 5; "digital health" = 3; "health services research" = 2; "health communication" = 1). Differences were found between the common understanding of DiPH in academia and the content in the module handbooks. The content identified in the analysis focuses mainly on technical areas. Social and health science content is only marginally present. DISCUSSION: The heterogeneous study programs with a connection to DiPH allow academic PH specialists to develop specific profiles. To achieve comprehensive competencies in DiPH, there is a need for further development of modules with relevance to the respective degree program. The results could be used for the (further) development of relevant modules and a core curriculum in DiPH.

Positive Aspects and Potential Drawbacks of Implementing Digital Teaching/Learning Scenarios in Health Professions Using Nursing Education as an Example: A Research Report from Germany.

BACKGROUND: Learning arrangements in health care profession education are increasingly taking place in digital environments. Virtual reality (VR) in nursing education, as a digital element, is the subject of controversial debate. On one hand, it supports the authenticity of case studies by adding realistic perspectives and information. On the other hand, the costs of developing and maintaining software and hardware hinder its long-term implementation. Based in the German context, our aim is to promote the adoption of innovative digital methods in nursing education and to offer invaluable experiences from the field. METHODS: In this paper, we describe our findings and insights from two different research projects focused on the incorporation of digital tools, particularly VR, into nursing education. RESULTS: Starting with a brief recapitulation of the projects, we elucidate pedagogical strategies for embedding VR-driven scenarios in nursing education. Based on our experiences during the projects, we identify various positive aspects, such as changing perspective and simulating acute situations. KEY FINDINGS: Although potential drawbacks remain, we advocate the long-term implementation and specific use of VR at the interface between theory and practice. Nevertheless, it is crucial to establish regular evaluation, observing the value of digitalisation, especially VR, for nursing education.

Molecular assessment of intratumoral immune cell subsets and potential mechanisms of resistance to odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

BACKGROUND: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1; NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab. METHODS: Patients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing. RESULTS: Baseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here. CONCLUSIONS: This biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.

From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma.

Molecular biology studies of uveal melanoma have resulted in the development of novel immunotherapy approaches including tebentafusp-a T cell-redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined immunotherapy is being developed as well as immunotherapy with bifunctional checkpoint inhibitory T cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination with IKKb-matured dendritic cells, or autologous dendritic cells loaded with autologous tumor RNA. Another potential approach to treat UM could be based on T cell receptor engineering rather than antibody modification. Immune-mobilizing monoclonal T cell receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, are promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis and therapy with the same molecule bring hope to this research.

Effectiveness of gamified digital interventions in mental health prevention and health promotion among adults: a scoping review.

BACKGROUND: Though still a young field of research, gamified digital interventions have demonstrated potential in exerting a favourable impact on health and overall well-being. With the increasing use of the internet and digital devices, the integration of game elements presents novel opportunities for preventing mental disorders and enhancing mental health. Hence, this review aims to assess the effectiveness of gamified interventions focusing on preventing mental disorders or promoting mental health among adults. METHODS: Based on a scoping review across four databases (MEDLINE, Embase, PsycInfo and Web of Science), 7,953 studies were initially identified. After removing duplicates and screening titles, abstracts and full texts, 16 studies were identified as suitable for inclusion in a narrative synthesis of findings. We included interventional studies encompassing an intervention and a control group aiming to investigate the effectiveness of the use of gamified digital mental health interventions and the use of gamified digital elements. RESULTS: Overall, positive effects of gamified interventions on mental health-related outcomes were identified. In particular, beneficial consequences for psychological well-being and depressive symptoms were observed in all studies. However, further outcomes, such as resilience, anxiety, stress or satisfaction with life, showed heterogenous findings. Most game elements used were reward, sensation and progress, whilst the quantity of elements was not consistent and, therefore, no substantiated conclusion regarding the (optimal) quantity or composition of game elements can be drawn. Further, the outcomes, measurements and analyses differed greatly between the 16 included studies making comparisons difficult. CONCLUSION: In summary, this review demonstrates the potential of integrating digital game elements on mental health and well-being with still a great gap of research. A taxonomy is needed to adequately address relevant game elements in the field of mental health promotion and prevention of mental disorders. Therefore, future studies should explicitly focus on the mechanisms of effect and apply rigorous study designs.

Anti-Inflammatory Activities of 8-Benzylaminoxanthines Showing High Adenosine A2A and Dual A1/A2A Receptor Affinity.

Chronic inflammation plays an important role in the development of neurodegenerative diseases, such as Parkinson's disease (PD). In the present study, we synthesized 25 novel xanthine derivatives with variable substituents at the N1-, N3- and C8-position as adenosine receptor antagonists with potential anti-inflammatory activity. The compounds were investigated in radioligand binding studies at all four human adenosine receptor subtypes, A1, A2A, A2B and A3. Compounds showing nanomolar A2A and dual A1/A2A affinities were obtained. Three compounds, 19, 22 and 24, were selected for further studies. Docking and molecular dynamics simulation studies indicated binding poses and interactions within the orthosteric site of adenosine A1 and A2A receptors. In vitro studies confirmed the high metabolic stability of the compounds, and the absence of toxicity at concentrations of up to 12.5 µM in various cell lines (SH-SY5Y, HepG2 and BV2). Compounds 19 and 22 showed anti-inflammatory activity in vitro. In vivo studies in mice investigating carrageenan- and formalin-induced inflammation identified compound 24 as the most potent anti-inflammatory derivative. Future studies are warranted to further optimize the compounds and to explore their therapeutic potential in neurodegenerative diseases.

The Potent and Selective Histamine H3 Receptor Antagonist E169 Counteracts Cognitive Deficits and Mitigates Disturbances in the PI3K/AKT/GSK-3ß Signaling Pathway in MK801-Induced Amnesia in Mice.

The role of histamine H3 receptors (H3Rs) in memory and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer's disease (AD), is well-accepted. Therefore, the procognitive effects of acute systemic administration of H3R antagonist E169 (2.5-10 mg/kg, i.p.) on MK801-induced amnesia in C57BL/6J mice using the novel object recognition test (NORT) were evaluated. E169 (5 mg) provided a significant memory-improving effect on MK801-induced short- and long-term memory impairments in NORT. The E169 (5 mg)-provided effects were comparable to those observed with the reference phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and were abrogated with the H3R agonist (R)-α-methylhistamine (RAMH). Additionally, our results demonstrate that E169 ameliorated MK801-induced memory deficits by antagonism of H3Rs and by modulation of the level of disturbance in the expression of PI3K, Akt, and GSK-3ß proteins, signifying that E169 mitigated the Akt-mTOR signaling pathway in the hippocampus of tested mice. Moreover, the results observed revealed that E169 (2.5-10 mg/kg, i.p.) did not alter anxiety levels and locomotor activity of animals in open field tests, demonstrating that performances improved following acute systemic administration with E169 in NORT are unrelated to changes in emotional response or in spontaneous locomotor activity. In summary, these obtained results suggest the potential of H3R antagonists such as E169, with good in silico physicochemical properties and stable retained key interactions in docking studies at H3R, in simultaneously modulating disturbed brain neurotransmitters and the imbalanced Akt-mTOR signaling pathway related to neurodegenerative disorders, e.g., AD.

Metabolic and cardiovascular benefits and risks of 4-hydroxy guanabenz hydrochloride: α2-adrenoceptor and trace amine-associated receptor 1 ligand.

BACKGROUND: α2-adrenoceptor ligands have been investigated as potential therapeutic agents for the treatment of obesity. Our previous studies have shown that guanabenz reduces the body weight of obese rats, presumably through its anorectic action. This demonstrates an additional beneficial effect on selected metabolic parameters, including glucose levels. The purpose of this present research was to determine the activity of guanabenz's metabolite-4-hydroxy guanabenz hydrochloride (4-OH-Guanabenz). METHODS: We performed in silico analyses, involving molecular docking to targets of specific interest as well as other potential biological targets. In vitro investigations were conducted to assess the selectivity profile of 4-OH-Guanabenz binding to α-adrenoceptors, along with intrinsic activity studies involving α2-adrenoceptors and trace amine-associated receptor 1 (TAAR1). Additionally, the effects of 4-OH-Guanabenz on the body weight of rats and selected metabolic parameters were evaluated using the diet-induced obesity model. Basic safety and pharmacokinetic parameters were also examined. RESULTS: 4-OH-guanabenz is a partial agonist of α2A-adrenoceptor. The calculated EC50 value for it is 316.3 nM. It shows weak agonistic activity at TAAR1 too. The EC50 value for 4-OH-Guanabenz calculated after computer simulation is 330.6 µM. Its primary mode of action is peripheral. The penetration of 4-OH-Guanabenz into the brain is fast (tmax = 15 min), however, with a low maximum concentration of 64.5 ng/g. 4-OH-Guanabenz administered ip at a dose of 5 mg/kg b.w. to rats fed a high-fat diet causes a significant decrease in body weight (approximately 14.8% compared to the baseline weight before treatment), reduces the number of calories consumed by rats, and decreases plasma glucose and triglyceride levels. CONCLUSIONS: The precise sequence of molecular events within the organism, linking the impact of 4-OH-Guanabenz on α2A-adrenoceptor and TAAR1 with weight reduction and the amelioration of metabolic disturbances, remains an unresolved matter necessitating further investigation. Undoubtedly, the fact that 4-OH-Guanabenz is a metabolite of a well-known drug has considerable importance, which is beneficial from an economic point of view and towards its further development as a drug candidate.

Impact of virtual reality applications in the treatment of anxiety disorders: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND AND OBJECTIVES: Anxiety disorders are the most prevalent mental disorders worldwide. Virtual reality (VR) treatment approaches have increasingly been studied. Before clinical implementation, it is necessary to evaluate the treatment effect of VR applications. The objective is to evaluate the treatment effect of virtual reality applications in the treatment of anxiety disorders compared to conventional therapy. METHODS: A systematic literature review with meta-analysis was conducted. Four databases were used to identify randomized controlled trials published between April 2011 and April 2021 which compare VR applications with non-VR interventions or waiting lists. Study characteristics, pre- and post-treatment data were extracted. Hedges g was calculated as effect size. Primary outcome was anxiety symptoms. RESULTS: Data from 17 studies from 827 participants was extracted. The studies examined specific phobia (n = 9), social anxiety disorder (n = 4), agoraphobia (n = 2) and panic disorder (n = 2). 16 out of 17 studies used head-mounted displays as VR application. A non-significant effect size with significant heterogeneity was observed in favor of the use of VR applications in anxiety symptoms (g, 0.33; 95%-CI, -0.20-0.87). Compared to passive control groups, VR applications are associated significant with lower anxiety symptoms (g, 1.29; 95%-CI, 0.68-1.90). LIMITATIONS: The study and patient characteristics varied between the individual studies which is reflected in a high statistical heterogeneity of the effect sizes. CONCLUSIONS: The added value of VR applications over waiting-list or psychoeducation only control groups is obvious. VR applications can be used as part of the treatment of anxiety disorders, especially when conventional therapy is unavailable.

Intratumoral dendritic cell-CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma.

Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). We leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC), as well as additional samples collected from patients treated off-label, to explore correlates of response to ICB within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+CH25H+IL-21+PD-1+CD4+ T helper cells ("CXCL13+ TH") and Granzyme K+ PD-1+ effector-like CD8+ T cells, whereas terminally exhausted CD39hiTOXhiPD-1hiCD8+ T cells dominated in nonresponders. CD4+ and CD8+ T cell clones that expanded post-treatment were found in pretreatment biopsies. Notably, PD-1+TCF-1+ (Progenitor-exhausted) CD8+ T cells shared clones mainly with effector-like cells in responders or terminally exhausted cells in nonresponders, suggesting that local CD8+ T cell differentiation occurs upon ICB. We found that these Progenitor CD8+ T cells interact with CXCL13+ TH within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ TH control the differentiation of tumor-specific Progenitor exhasuted CD8+ T cells following ICB.

Integration of the Vision of People With Diabetes Into the Development Process to Improve Self-management via Diabetes Apps: Qualitative Interview Study.

BACKGROUND: Diabetes is a major global epidemic and serious public health problem. Diabetes self-management is a 24/7 challenge for people with type 1 diabetes that influences their quality of life (QoL). Certain apps can support the self-management of people with diabetes; however, current apps do not meet the needs of people with diabetes appropriately, and their safety is not ensured. Moreover, there are a multitude of hardware and software problems associated with diabetes apps and regulations. Clear guidelines are required to regulate medical care via apps. In Germany, apps must undergo 2 examination processes to be listed in the Digitale Gesundheitsanwendungen directory. However, neither examination process considers whether the medical use of the apps is sufficient for users' self-management. OBJECTIVE: This study aims to contribute to the technology development process of diabetes apps by exploring individual perspectives on desired features and content of diabetes apps among people with diabetes. The vision assessment conducted is a first step toward creating a shared vision among all relevant stakeholders. To ensure adequate research and development processes for diabetes apps in the future, guiding visions from all relevant stakeholders are required. METHODS: In a qualitative study, 24 semistructured interviews with patients with type 1 diabetes were conducted, among whom 10 (42%) were currently using an app. To clarify the perceptions of people with diabetes regarding the functions and content of diabetes apps, a vision assessment was conducted. RESULTS: People with diabetes have concrete ideas of features and content in apps to improve their QoL and allow them to live as comfortably as possible, such as informative predictions through artificial intelligence, improvements in signal loss and value delay through smartwatches, improved communication and information-sharing capabilities, reliable information sources, and user-friendly and discreet messaging options through smartwatches. In addition, according to people with diabetes, future apps should show improved sensors and app connectivity to avoid incorrect values being displayed. They also wish for an explicit indication that displayed values are delayed. In addition, personalized information was found to be lacking in apps. CONCLUSIONS: People with type 1 diabetes want future apps to improve their self-management and QoL and reduce stigma. Desired key features include personalized artificial intelligence predictions of blood glucose levels, improved communication and information sharing through chat and forum options, comprehensive information resources, and smartwatch alerts. A vision assessment is the first step in creating a shared vision among stakeholders to responsibly guide the development of diabetes apps. Relevant stakeholders include patient organizations, health care professionals, insurers, policy makers, device manufacturers, app developers, researchers, medical ethicists, and data security experts. After the research and development process, new apps must be launched while considering regulations regarding data security, liability, and reimbursement.

The untapped potential of Games for Health in times of crises. A critical reflection.

Given its promising role in public health to address hard to reach population groups, game-based interventions (i.e., Games for Health, G4H) have experienced growing interest in recent years. Therefore, it is surprising that they have played only a minor role during the COVID-19 pandemic. Hence, the aim of this paper is to reflect the opportunities and challenges of G4H especially during the pandemic but also with regard to future health crises. As commercial video games (i.e., those that primarily aim to entertain its users) were often used to deal with the containment measures during the COVID-19 pandemic, we call for greater cooperation with commercial game makers to distribute health-related messages via entertainment games. With regard to G4H we see a need to (i) strengthen the intervention theory underlying game-based applications, (ii) to enhance the appeal of games in order to maintain the interest of users in the long term, and (iii) to improve the evidence base using appropriate study designs. Finally, we argue for (iv) greater user involvement, both in terms of developing game-based approaches and as co-researchers in solving complex health problems.

Pregnancy Care during the COVID-19 Pandemic in Germany: A Public Health Lens.

The COVID-19 pandemic has led to various challenges in German health care, including pregnancy care. This paper aims to provide an overview of the pandemic-related challenges faced by pregnant women, new mothers, and their families in maternal and newborn care. A literature review was performed by including international literature as well as recommendations of institutions and official stakeholders. These challenges refer to restrictions at all stages of pregnancy, including wearing masks during labour, limitations of a companion of choice during birth, and restrictions of unvaccinated women from attending, e.g., antenatal classes. Compared with the general population, COVID-19 vaccination of pregnant women was recommended later, as pregnant women were initially excluded from clinical trials. Women who gave birth during the COVID-19 pandemic also reported mental health issues. The findings stress the importance of the inclusion of pregnant women in clinical trials. This might also help to overcome vaccine hesitancy among pregnant women and women seeking family planning. Taking the COVID-19 pandemic as an example, one must weigh the changes and restrictions associated with the potential disadvantages for mothers, newborns, and their families in pregnancy care against the measures to control the pandemic.

Hosting an Online World Café to Develop an Understanding of Digital Health Promoting Settings from a Citizen's Perspective-Methodological Potentials and Challenges.

Brown and Isaacs' World Café is a participatory research method to make connections to the ideas of others. During the SARS-CoV-2 pandemic and the corresponding contact restrictions, only digital hostings of World Cafés were possible. This article aims to present and reflect on the potentials and challenges of hosting online World Cafés and to derive recommendations for other researchers. Via Zoom and Conceptboard, three online World Cafés were conducted in August 2021. In the World Cafés, the main focus was on the increasing digitization in settings in the context of health promotion and prevention from the perspective of setting members of educational institutions, leisure clubs, and communities. Between 9 and 13 participants participated in three World Cafés. Hosting comprises the phases of design and preparation, realisation, and evaluation. Generally, hosting an online World Café is a suitable method for participatory engagement, but particular challenges have to be overcome. Overall café hosts must create an equal participation environment by ensuring the availability of digital devices and stable internet access. The event schedule must react flexibly to technical disruptions and varying participation numbers. Further, compensatory measures such as support in the form of technical training must be implemented before the event. Finally, due to the higher complexity of digitalisation, roles of participants and staff need to be distributed and coordinated.

Structure Prediction, Evaluation, and Validation of GPR18 Lipid Receptor Using Free Programs.

The GPR18 receptor, often referred to as the N-arachidonylglycine receptor, although assigned (along with GPR55 and GPR119) to the new class A GPCR subfamily-lipid receptors, officially still has the status of a class A GPCR orphan. While its signaling pathways and biological significance have not yet been fully elucidated, increasing evidence points to the therapeutic potential of GPR18 in relation to immune, neurodegenerative, and cancer processes to name a few. Therefore, it is necessary to understand the interactions of potential ligands with the receptor and the influence of particular structural elements on their activity. Thus, given the lack of an experimentally solved structure, the goal of the present study was to obtain a homology model of the GPR18 receptor in the inactive state, meeting all requirements in terms of protein structure quality and recognition of active ligands. To increase the reliability and precision of the predictions, different contemporary protein structure prediction methods and software were used and compared herein. To test the usability of the resulting models, we optimized and compared the selected structures followed by the assessment of the ability to recognize known, active ligands. The stability of the predicted poses was then evaluated by means of molecular dynamics simulations. On the other hand, most of the best-ranking contemporary CADD software/platforms for its full usability require rather expensive licenses. To overcome this down-to-earth obstacle, the overarching goal of these studies was to test whether it is possible to perform the thorough CADD experiments with high scientific confidence while using only license-free/academic software and online platforms. The obtained results indicate that a wide range of freely available software and/or academic licenses allow us to carry out meaningful molecular modelling/docking studies.

Imaging of Uveal Melanoma-Current Standard and Methods in Development.

Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients' chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.

Role of positive mental health in reducing fears related to COVID-19 and general anxiety disorder in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: The outbreak of the novel coronavirus disease (COVID-19) has posed multiple challenges to healthcare systems. Evidence suggests that mental well-being is badly affected due to compliance with preventative measures in containing the COVID-19 pandemic. This study aims to explore the role of positive mental health (subjective sense of wellbeing) to cope with fears related to COVID-19 and general anxiety disorder in the Pashtun community in Pakistan. METHODS: A cross-sectional survey was conducted among 501 respondents from Khyber Pakhtunkhwa participating in an online-based study. We performed correlational analysis, hierarchical linear regression and structural equational modeling (SEM) to analyze the role of mental health in reducing fears and general anxiety disorder. RESULTS: The results of the SEM show that positive mental health has direct effects in reducing the fear related to COVID-19 (ß = - 0.244, p < 0.001) and general anxiety (ß = - 0.210, p < 0.001). Fears of COVID-19 has a direct effect on increasing general anxiety (ß = 0.480). In addition, positive mental health also has an indirect effect (ß = - 0.117, p < 0.001) on general anxiety (R2 = 0.32, p < 0.001) through reducing fear of coronavirus. CONCLUSION: Based on these findings, there is a need to develop community health policies emphasizing on promotive and preventive mental health strategies for people practicing social/physical distancing.