Cardiovascular disease remains a leading cause of morbidity and mortality in people with types 1 or 2 diabetes mellitus. Although beneficial roles for strict control of hyperglycemia have been ...suggested, such a strategy is not without liabilities. Specifically, the risk of hypoglycemia and its consequences remain an omnipresent threat with such approaches. The advent of the CVOT (Cardiovascular Outcomes Trials) for new antidiabetes mellitus treatments has uncovered unexpected benefits of cardiovascular protection in some of the new classes of agents, such as the GLP-1 RAs (glucagon-like peptide-1 receptor agonists) and the SGLT-2 (sodium-glucose cotransporter-2) inhibitors. Further, state-of-the-art approaches, such as antibodies to PCKSK9 (proprotein convertase subtilisin-kexin type 9); RNA therapeutics; agents targeting distinct components of the immune/inflammatory response; and novel small molecules that block the actions of RAGE (receptor for advanced glycation end products) signaling, also hold potential as new therapies for diabetes mellitus and cardiovascular disease. Finally, interventions such as weight loss, through bariatric surgery, may hold promise for benefit in diabetes and cardiovascular disease. In this Brief Review, some of the novel approaches and emerging targets for the treatment of diabetes mellitus and cardiovascular disease are discussed. Ultimately, identification of the optimal timing and combinations of such interventions, especially in the context of personalized approaches, together with emerging disease-modifying agents, holds great promise to reduce the burden that diabetes poses to the cardiovascular system.
Recent theory on narrative processes suggests that changes in recipients' emotional responses (emotional shifts) are characteristic of immersed story processing and precursors of narrative impact. In ...two experiments and a pilot study, a novel self-probed emotional retrospection task was used to measure emotional shifts. We examined the link between transportation and emotional shifts and the association of these processes with story-consistent attitudes, social sharing intentions, and behavior. We manipulated transportation via positive and negative reviews prior to story exposure. Consistent with theory, and across both experiments, we found that transportation was positively associated with the number and intensity of emotional shifts. Transportation was linked to affective-level attitudes in particular. While emotional shifts were not related to attitudes in Experiment 1, they were related to affective-level attitudes and social sharing intentions in Experiment 2. We further discuss the validity of emotional shifts measured through self-probed retrospections in light of the results of the presented studies.
The United States Food and Drug Administration, the first regulatory authority to approve CAB-LA, recommends nucleic acid amplification testing (NAAT) prior to initiation and follow-up. ...as ...confirmatory HIV testing is required for diagnosis, earlier detection with NAAT may not result in an earlier diagnosis. ...NAATs are not readily available in many LMICs, as most do not have regulatory approval for HIV diagnosis.Comparatively long turnaround times and higher costs limit the feasibility of this approach. The risk of delayed identification of HIV infection and potential increase in HIV drug resistance (theoretically prevented with NAAT) must be balanced with the benefits of wider CAB-LA access and decreasing new HIV infections (using current national testing algorithms).
•Digital platforms extensively transform business models in Industry 4.0 contexts.•Especially value propositions, revenue streams, and key partners are changed.•Inter-company and customer ...relationships also undergo significant alterations.•The results vary between different industry sectors and company sizes.•An ecosystem perspective enables a differentiation between platform roles and types.
Being successfully applied in business-to-consumer industries for quite some time, digital platforms only recently have found their way into the industrial business-to-business world. However, rapid developments, particularly in the context of Industry4.0, have indicated enormous potentials from digital platforms for business models and inter-company relationships – fields of particular importance in industrial marketing. Motivated by a lack of empirical insights and calls from academia and practice, this paper sheds light on how digital platforms change industrial firms’ business models and inter-company relationships. We applied an exploratory case study design and analyzed a unique sample of 11 platform cases from the United States and Germany, differentiating between platform types and roles. The study reveals recurring themes in business model innovation and inter-company relationships. The results were elicited using a quasi-statistical approach, discussed and interpreted against the backdrop of the current state of research on platforms, business models, and industrial marketing.
Introduction
Pre‐exposure prophylaxis (PrEP) is an important HIV prevention option. Two randomized trials have provided efficacy evidence for long‐acting injectable cabotegravir (CAB‐LA) as PrEP. In ...considering CAB‐LA as an additional PrEP modality for people at substantial risk of HIV, it is important to understand community response to injectable PrEP. We conducted a systematic review of values, preferences and perceptions of acceptability for injectable PrEP to inform global guidance.
Methods
We searched nine databases and conference websites for peer‐reviewed and grey literature (January 2010−September 2021). There were no restrictions on location. A two‐stage review process assessed references against eligibility criteria. Data from included studies were organized by constructs from the Theoretical Framework of Acceptability.
Results
We included 62 unique references. Most studies were observational, cross‐sectional and qualitative. Over half of the studies were conducted in North America. Men who have sex with men were the most researched group. Most studies (57/62) examined injectable PrEP, including hypothetical injectables (55/57) or placebo products (2/57). Six studies examined CAB‐LA specifically. There was overall interest in and often a preference for injectable PrEP, though there was variation within and across groups and regions. Many stakeholders indicated that injectable PrEP could help address adherence challenges associated with daily or on‐demand dosing for oral PrEP and may be a better lifestyle fit for individuals seeking privacy, discretion and infrequent dosing. End‐users reported concerns, including fear of needles, injection site pain and body location, logistical challenges and waning or incomplete protection.
Discussion
Despite an overall preference for injectable PrEP, heterogeneity across groups and regions highlights the importance of enabling end‐users to choose a PrEP modality that supports effective use. Like other products, preference for injectable PrEP may change over time and end‐users may switch between prevention options. There will be a greater understanding of enacted preference as more end‐users are offered anti‐retroviral (ARV)‐containing injectables. Future research should focus on equitable implementation, including real‐time decision‐making and how trained healthcare providers can support choice.
Conclusions
Given overall acceptability, injectable PrEP should be included as part of a menu of prevention options, allowing end‐users to select the modality that suits their preferences, needs and lifestyle.
Globally, obesity is on the rise. Research over the past 20 years has highlighted the far-reaching multisystem complications of obesity, but a better understanding of its complex pathogenesis is ...needed to identify safe and lasting solutions.
Abstract Emerging evidence links the receptor for advanced glycation endproducts (RAGE) to the pathogenesis of tissue damage in chronic metabolic and inflammatory diseases. In human subjects, ...multiple reports suggest that in the plasma/serum, circulating levels of distinct forms of soluble RAGEs may be biomarkers of the presence or absence, and the extent of chronic disease. These considerations prompt us to consider in this review, what are soluble RAGEs; how are they formed; what might be their natural functions; and may they serve as biomarkers of inflammatory and metabolic disease activity? In this brief review, we seek to address what is known and suggest new areas for scientific investigation to uncover the biology of soluble RAGEs.
Amyloid formation by the neuropancreatic hormone, islet amyloid polypeptide (IAPP or amylin), one of the most amyloidogenic sequences known, leads to islet amyloidosis in type 2 diabetes and to islet ...transplant failure. Under normal conditions, IAPP plays a role in the maintenance of energy homeostasis by regulating several metabolic parameters, such as satiety, blood glucose levels, adiposity and body weight. The mechanisms of IAPP amyloid formation, the nature of IAPP toxic species and the cellular pathways that lead to pancreatic β-cell toxicity are not well characterized. Several mechanisms of toxicity, including receptor and non-receptor-mediated events, have been proposed. Analogs of IAPP have been approved for the treatment of diabetes and are under investigation for the treatment of obesity.
Emotional shifts in stories are assumed to contribute to narrative persuasion by enhancing engagement with the story. This effect might depend on the congruency of audiences' emotional experience to ...the emotions implied by the story. In two experiments with wellcontrolled story manipulations, we compared the persuasive effect of stories with shifts in valence (from positive to negative to positive) to continuously positive story versions and examined moderating influences of event-congruent emotions and narrative transportation. The positive story versions were consistently more persuasive than the versions with emotional shifts. Transportation increased the persuasive effect of the stories, but only in audiences that listened to the shifting stories. In both emotional story trajectories, event-congruent emotional experience enhanced persuasion. We discuss our findings in terms of boundary conditions of the effect of emotional shifts in narrative persuasion.
The underlying motivation of this work is to demonstrate that artificial muscle activity of known and unknown motion can be generated based on motion parameters, such as angular position, ...acceleration, and velocity of each joint (or the end-effector instead), which are similarly represented in our brains. This model is motivated by the known motion planning process in the central nervous system. That process incorporates the current body state from sensory systems and previous experiences, which might be represented as pre-learned inverse dynamics that generate associated muscle activity.
We develop a novel approach utilizing recurrent neural networks that are able to predict muscle activity of the upper limbs associated with complex 3D human arm motions. Therefore, motion parameters such as joint angle, velocity, acceleration, hand position, and orientation, serve as input for the models. In addition, these models are trained on multiple subjects (n=5 including , 3 male in the age of 26±2 years) and thus can generalize across individuals. In particular, we distinguish between a general model that has been trained on several subjects, a subject-specific model, and a specific fine-tuned model using a transfer learning approach to adapt the model to a new subject. Estimators such as mean square error MSE, correlation coefficient r, and coefficient of determination R
are used to evaluate the goodness of fit. We additionally assess performance by developing a new score called the zero-line score. The present approach was compared with multiple other architectures.
The presented approach predicts the muscle activity for previously through different subjects with remarkable high precision and generalizing nicely for new motions that have not been trained before. In an exhausting comparison, our recurrent network outperformed all other architectures. In addition, the high inter-subject variation of the recorded muscle activity was successfully handled using a transfer learning approach, resulting in a good fit for the muscle activity for a new subject.
The ability of this approach to efficiently predict muscle activity contributes to the fundamental understanding of motion control. Furthermore, this approach has great potential for use in rehabilitation contexts, both as a therapeutic approach and as an assistive device. The predicted muscle activity can be utilized to guide functional electrical stimulation, allowing specific muscles to be targeted and potentially improving overall rehabilitation outcomes.
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