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Theory of mind is an essential ability for complex social interaction and collaboration. Researchers in cognitive science and psychology have previously sought to integrate theory of mind capabilities into artificial intelligence (AI) agents to improve collaborative abilities (Cuzzolin, Morelli, Cirstea, & Sarahakian, 2020). We introduce the Recurrent Conditional Variational Autoencoder (RCVAE), a novel model which leverages the ability of generative models to learn rich abstracted representations of contextual behaviors to predict behavioral intent from human behavioral trajectories. Advancing on current concept learning models, this model allows for the discovery of latent intent in human behavior trajectories, while maintaining the scalability and performance of generative AI models. We show that in the Overcooked-AI environment, the RCVAE outperforms baseline Long Short-Term Memory (LSTM) models in predicting intent, achieving higher prediction accuracy and greater predictive stability. The implications of these results are significant; the RCVAE's proficiency in learning the relationship between basic actions and resulting contextual behaviors represents a significant advancement in concept learning for behavioral intent prediction.

Introduction: The abrupt transition to remote learning caused by the COVID-19 pandemic clearly indicated the need to implement radical technological and institutional changes to the current approach to teaching. Virtual reality (VR) and artificial intelligence (AI) assisted programs have emerged as the new and effective methods utilized in education and medical training. Material and methods: The Virtual Clinic (VC) is a new online application developed by Polish medical universities which implement AI algorithms to teach students the medical interview including obtaining patients medical history, performing a physical examination as well as diagnostics and treatment planning. Our study enrolled 164 medical students who tested the VC and completed an online questionnaire. Results: The results of the survey showed that 93.9% of the respondents believe that the VC will prove effective as an educational tool supporting teaching at faculties of medicine and health sciences. Conclusions: Our preliminary experiences suggest that the use of AI assisted programs such as the VC seems highly anticipated and justified in medical higher education.

Abstract Background Focal epilepsy is common in children and adults with mitochondrial disease. Seizures are often refractory to pharmacological treatment and, in this patient group, frequently evolve to refractory focal status epilepticus (also known as epilepsia partialis continua). Where this occurs, the long-term prognosis is poor. Transcranial DC stimulation (tDCS) is a promising, non-invasive, adjunctive treatment alternative to common surgical procedures. Limited recruitment of study participants with this rare disease and the ethical challenges of administering a treatment to one group and not another, while maintaining strict methodological rigour can pose challenges to the design of a clinical study. Method We designed the first delayed start, double-blinded, sham-controlled study to evaluate the efficacy of tDCS as an adjunctive treatment for focal epilepsy. We will include participants with a genetically confirmed diagnosis of mitochondrial disease with drug-resistant focal epilepsy aged ≥ 2 years, aiming to collect 30 episodes of focal status epilepticus, each treated for a maximum period of 14 days. The early start intervention arm will receive tDCS from day 1. The delayed start intervention arm will receive sham stimulation until crossover on day 3. Our primary endpoint is a greater than 50% reduction from baseline (on day 0) in seizure frequency assessed by 3x daily reporting, accelerometery, and video monitoring. Changes in the underlying epileptogenic focus within the brain related to the tDCS intervention will be assessed by magnetic resonance imaging (MRI) and/or electroencephalography (EEG). Discussion Study results in favour of treatment efficacy would support development of tDCS into a mainstream treatment option for focal epileptic seizures related to mitochondrial disease. Trials registration ISRCTN: 18,241,112; registered on 16/11/2021.

Abstract Background The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of parents of reproductive age consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on foetal growth and development and ultimately impact the long-term adult health of the offspring. In this study, we examined sperm- and seminal vesicle fluid-mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Results Male mice were fed a diet to model either under (low-protein diet (LPD)) or over (high-fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl donors or a control diet (CD) before mating with age-matched females. Male metabolic health was influenced by WD and MD-WD, with significant changes in multiple serum lipid classes and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35 transcripts). Separate analysis of the seminal vesicle fluid proteome revealed a significant number of differentially expressed proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. Following mating, in vitro time-lapse imaging of preimplantation embryos revealed a significant increase in the timing of development in all experimental groups when compared to CD embryos. Finally, qPCR analysis of uterine tissue at the time of implantation identified perturbed expression of Cd14 and Ptgs1 following mating with WD-fed males. Conclusions Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive health, impacting on embryonic development and the maternal reproductive tract. This study highlights potential direct (sperm-mediated) and indirect (seminal vesicle fluid-mediated) pathways in which a father’s poor diet could shape the long-term health of his offspring.

Student wellbeing is a key concern for those delivering tertiary education. Tertiary providers such as universities use a range of techniques to support student wellbeing through times of stress. This article reports on one finding from a mixed methods study at two New Zealand universities that explored how students enrolled in agricultural courses saw and managed their wellbeing. The findings demonstrated that students reflected an optimism bias regarding managing their own stress believing most stressful situations would resolve without the need to involve support services. Their intent was that university support services were only to be used in times of mental health crisis. Consequently, students reported that they would not engage with support and education around managing their wellbeing but did find value in learning about how to support others through times of crisis. These findings contribute to knowledge about tertiary students' attitudes to stress and support services. They have implications for those delivering wellbeing services at tertiary institutions in terms of how best to tailor and deliver services for students experiencing stress.

Background: As the burden of mental health challenges increases globally, delivering mental health education programmes to at-risk groups is critical. Important factors governing the success of health and wellbeing education include the relationships and connections formed between students and those delivering the education. This article reports on the qualitative findings from a mixed-methods study evaluating a mental health wellbeing programme delivered to first-year agricultural students across two universities in New Zealand. Design: The qualitative data that formed the basis of this article involved an exploratory approach utilising semi-structured interviews with participants who had attended a mental health wellbeing programme. Findings: The study found that feelings of connectedness in relation to the programme and the educators, as well as the material provided, improved engagement. In particular, connection was improved through the use of peer educators from within the target community, alongside considerations of timing, promotion and incentives in the delivery of programmes. Conclusions: Relationships and building connections are crucial when delivering health and wellbeing education. These findings have implications for those developing and delivering educational mental health interventions at tertiary institutions in terms of the mechanisms used to support engagement, learning and integration of knowledge.

This study aimed to evaluate the effectiveness of an automated tail movement sensor device (Moocall; Bluebell, Dublin, Ireland) to predict time of calving in dairy cows. At a commercial dairy farm in southern Ontario, Moocall (MC) devices were attached with the device's strap, and an additional elastic wrap, to the tail of cows approximately 3 d before their expected calving date. The MC has 2 types of alarm, a high activity alarm in the previous hour (1HA), and a high activity alarm in the previous 2 h (2HA); these alarms were sent and registered to the MC software. The calving and close-up pens were video monitored to determine the exact time of the onset of stage II of calving (amniotic sac visible at the vulva) and the end of stage II of calving (total expulsion of the calf). A total of 49 cows were enrolled, but we excluded 13 animals from the analysis as they had 3 or more MC drops from the tail (n = 6), a swollen tail (n = 3), or the MC device was lost (n = 4); this left 36 cows. In total, the device dropped off 21 (42%) cows. The average number of alarms (1HA and 2HA) per cow before stage II of calving was 2.7 ± 2.3 (± standard error). The first alarm after fitting the device on the tail was used to determine the device's sensitivity and specificity. Depending on the interval before the onset of parturition (i.e., 2, 4, 8, 12 h) in which the alarm was triggered, sensitivity varied from 5% to 72% and specificity from 50% to 93%. The false positive rate varied between 6% and 50% depending on the interval from the alarm to the onset of parturition. The high false positive and device drop rates (despite the addition of the elastic wrap) may compromise the applicability of this sensor device in a commercial setting.

ABSTRACT: The objective of this review was to outline current implementation of biosecurity, the impact of biosecurity on the industry, and producers' and veterinarians' perceptions of biosecurity, with a focus on the Canadian dairy industry. Biosecurity has an important role in farm safety by reducing the spread of pathogens and contaminants, improving animal health and production, and maintaining human safety. Implementation of biosecurity practices varies among farms and countries. Because Canada's supply management system is different than other countries, different barriers and perceptions of biosecurity may exist. Producers may have negative perspectives on biosecurity, such as it being expensive or time consuming. Producers are motivated or deterred from biosecurity implementation for many reasons, including perceived value, disease risk, and financial incentives or deterrents. In addition, because veterinarians are a trusted source of information, their approaches to discussions on biosecurity implementation are important to understand. Veterinarians and producers appear to have differing opinions on the importance of biosecurity and approaches to discussing biosecurity. Improving biosecurity implementation requires a multifactorial approach, such as individualized education and awareness for producers, further research into efficacy of and barriers to biosecurity, and development of strategies for effective communication between veterinarians and producers.

Abstract Understanding species phenology and temporal co‐occurrence across trophic levels is essential to assess anthropogenic impacts on ecological interactions. We analyzed 15 yr of monitoring data to identify trends and drivers of timing and magnitude of bloom‐forming phytoplankton and diverse zooplankton taxa in the central Baltic Sea. We show that the timings of phytoplankton blooms advance, whereas crustacean zooplankton seasonal timings remain constant. This increasing offset with the spring bloom is linked to the decline of Pseudocalanus, a key copepod sustaining pelagic fish production. The majority of copepod and cladoceran taxa, however, are co‐occurring with summer blooms. We also find new developing fall blooms, fueling secondary production later in the season. Our study highlights that response to climate change differs within and between functional groups, stressing the importance of investigating plankton phenologies over the entire annual cycle in pelagic systems.

Background Current National Health Service policy in England encourages enhanced digital access in primary care service provision. In this study, we investigate ‘digital facilitation’ – that range of processes, procedures and personnel which seeks to support National Health Service primary care patients in their uptake and use of online services. Objectives Identify, characterise and explore the potential benefits and challenges associated with different models of digital facilitation currently in use in general practice which are aimed at improving patient access to online services in general practice in England. Use the resulting intelligence to design a framework for future evaluations of the effectiveness and cost effectiveness of such interventions. Explore how patients with mental health conditions experience digital facilitation and gauge their need for this support. Design Observational mixed-methods study (literature review, surveys, ethnographic observation and interviews); formal synthesis of findings. Setting General practice in four regions of England. Participants Practice survey: 156 staff. Patient survey: 3051 patients. Mental health survey: 756 patients. General practitioner patient survey: 3 million responders. Ethnographic case-studies: 8 practices; interviews with 36 staff, 33 patients and 10 patients with a mental health condition. Stakeholder interviews: 19 participants. Intervention Digital facilitation as undertaken in general practice. Main outcome measures Patient and practice staff reported use of, and views of, digital facilitation. Data sources Surveys, qualitative research; national General Practitioner Patient Survey (2019–22). Review methods Scoping-review methodology applied to academic and grey literature published 2015–20. Results While we did find examples of digital facilitation in routine practice, these often involved using passive or reactive modes of support. The context of COVID, and the necessary acceleration (at that time) of the move to a digital-first model of primary care, shaped the way digital facilitation was delivered. There was lack of clarity over where the responsibility for facilitation efforts lay; it was viewed as the responsibility of ‘others’. Patients living with mental health conditions had similar needs and experiences regarding digital facilitation to other patients. Limitations The context of the COVID pandemic placed limitations on the project. Fewer practices responded to the practice survey than anticipated; reconfiguration of general practices to support COVID measures was a key consideration during non-participant observation with social distancing and other measures still in place during fieldwork. Conclusions Digital facilitation, while not a widely recognised concept, is important in supporting the move to a National Health Service with enhanced digital opportunities and enhanced digital access. General practice staff are allocating resources to provide such efforts in general practices in England. The establishment of clear lines of responsibility, the development of digital tools and platforms that work for patients and practice staff, and investment in staff time and training are needed if digital facilitation is to support the intended digital revolution. Future work We did not find one single dominant or preferred model of digital facilitation which might reasonably be considered to form the basis of an intervention to be tested. Rather, there is a need to co-develop such an intervention with patients, general practice staff and relevant policy experts. We outline a framework for a future evaluation of such an intervention. Study registration This study is registered as ResearchRegistry6523 (www.researchregistry.com/browse-the-registry#home/?view_2_search=Di-Facto&view_2_page=1) and PROSPERO CRD42020189019 (www.crd.york.ac.uk/prospero/display_record.php?RecordID=189019). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128268) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 32. See the NIHR Funding and Awards website for further award information. Plain language summary Background Online services are common in the National Health Service. This research looked at ‘digital facilitation’ in general practices. Digital facilitation is about supporting National Health Service patients in their use of online services. We aimed to understand how much digital facilitation is being used by general practices. We also looked at how digital facilitation happens and if it affects the number of people using online services. Methods We looked at previous research to help us understand what approaches have been used to support patients to use online services. We used surveys to ask staff at general practices what they were already doing, and to ask patients about their experiences. We observed digital facilitation in general practices and spoke to patients and staff to help us understand the benefits and challenges of different approaches. We combined findings from the three stages outlined above to identify key aspects of digital facilitation. All stages of our research included discussions with the project’s patient advisory group. Key findings We found that digital facilitation is seen as important and has many forms. Most general practices are using passive and reactive types of facilitation. An example of passive facilitation, initiated by the service but not involving direct inter-personal interaction, is the use of text messaging relating to ordering of repeat prescriptions online. An example of reactive facilitation is providing a response to a patient-initiated query regarding online access. There is clear scope to develop a more proactive approach to facilitation that actively engages patients. Our research highlights a lack of clarity over who is responsible for digital facilitation. Different people (patients, staff, policy-makers) often think that the responsibility lies with others. Investment in digital facilitation is needed. Tools and platforms for digital facilitation that meet patients’ and general practices’ needs should be developed. Scientific summary Background The NHS is facing the increasing demands of a growing and ageing population, technological progress and changing public expectations. Current NHS policy in England encourages enhanced digital opportunities and enhanced digital access in primary care provision. Drivers behind this move include the assumption that online services lead to improved choice, convenience, and ease of access for users, improved triage systems and streamlining of service delivery. In this research, we addressed ‘digital facilitation’ [digital facilitation (DF)] – ‘that range of processes, procedures and personnel which seeks to support NHS patients in their uptake and use of online services’. We investigated the provision by general practices to support access to NHS online primary care services by their registered patients and carers of those patients. Support in accessing and using services is required at all stages: initial registration for online services; subsequent continued use; and navigating the wide range of NHS online provision. Hence, it is important to understand the extent to which approaches to DF are applied, how they are applied, the impact such efforts have on uptake of online services, and how such uptake may affect patient health and access to healthcare information and services. Aims Identify, characterise and explore the potential benefits and challenges associated with different models of DF currently in use in general practice in England which are aimed at improving patient access to online primary care services. Use the resulting intelligence to design a framework for future evaluations of the effectiveness and cost effectiveness of such interventions. Explore how patients with mental health conditions experience DF and gauge their need for this support. Methods The project comprised four interlinked elements. Initially we undertook a scoping review and narrative synthesis of published literature, seeking to understand and characterise the range, effectiveness and cost effectiveness of models of DF for improving access to online services within health. Searches of academic databases and grey literature published between 2015 and 2020 were undertaken, including snowballing from the publications they cited. We surveyed general practice staff and patients (with an additional boost sample of patients living with mental health conditions, which was in direct response to a National Institute for Health and Care Research commissioning brief) and undertook analyses of data from the national General Practice Patient Survey (GPPS). The practice staff questionnaire included items addressing which online services were being used and what steps had been implemented in practices to promote and support the use of such services. We implemented a sequential mixed mode when inviting staff from 500 general practices to complete the survey online or on paper. The patient questionnaire addressed patients’ familiarity and confidence with information technology (IT) and internet use, their awareness and uptake of online services, and their experiences of any support provided by their practice. Questionnaires were sent by post with the option of replying online or by post. We also analysed responses to questions from the English national GPPSs (2019–22) concerning awareness and use of online booking of appointments, ordering repeat prescriptions and accessing medical records, and additionally the use of online consultations. Logistic regression models were used to examine how the awareness and use of online services, the awareness and use of facilitation efforts, and experience of other support varied by patient characteristics. We undertook a qualitative exploration of DF comprising two elements: focused ethnographic case studies in general practices, and an interview study with key stakeholders. Focused ethnography was used to explore, in-depth, the use of DF in general practices. Eight general practice case study sites were recruited to provide variation in terms of their DF offering, and in terms of a range of practice characteristics (practice setting, deprivation status and size, and the age profile of registered patients). We undertook: non-participant observation of the process of DF and how practice staff and patients/carers interact with different types of DF, semistructured interviews with staff members and patients in each practice, and collected secondary analysis of documentation pertaining to digital services or facilitation within the practice. This was augmented by 10 interviews with patients living with mental health conditions from the case study sites; these sought to explore their experiences of DF. The interview study with key stakeholders sought understanding of the broader context and wider drivers of DF in primary care. We conducted semistructured interviews with stakeholders providing a level of insight beyond individual practices, including policy-makers, commissioners and third- sector organisations. Data from the focused ethnographic case studies and stakeholder interviews were analysed together using thematic analysis. We conducted a synthesis of the evidence generated by each element of the study. We employed Weiss’s approach to theory-based evaluation as a theoretical framework. A pragmatic, iterative and cumulative approach was applied to synthesising the findings from all elements and to developing programme and implementation theories. We triangulated findings, summarising the results in a matrix, which evolved into thematic groupings as the study progressed and as evidence from our work packages (WPs) became available. Findings were brought together in a series of three workshop meetings of researchers and patient/public participants as individual WPs were completed. The synthesis process concluded following an online discussion with national and regional stakeholders. We used the synthesised findings to identify the key aspects of a framework aimed at informing future research on DF. Patient and public involvement and engagement (PPIE) was embedded throughout this research, from the original conception through to the design and conduct of the research, and the synthesis and interpretation of findings. Our team has benefited from a patient co-investigator, a dedicated PPIE co-ordinator, and an actively engaged Patient Advisory Group (PAG). All WPs have worked with the PAG to ensure the research is patient focused and addresses patient needs. The PAG was augmented with additional members with lived experience of mental health conditions to ensure that the additional work focused on patients living with mental health conditions was appropriately framed. Members of the PAG were fully involved as equal voices alongside the research team in the synthesis workshops. Results The synthesis of findings from the literature review, surveys and qualitative work resulted in the identification of 11 thematic groups (distinct from, but incorporating, the results of the qualitative thematic analysis): 3 scene-setting themes relating to the context in which DF takes place, and 8 themes related to types of DF, their implementation and effectiveness. Scene-setting themes: The first theme related to the value and purpose of digital services. The qualitative exploration found that the need for, and value of, digital services are not always clear and that there is a lack of shared understanding or belief about what digital services should achieve. The second theme related to conflation of the digital environment with other routes to access. For example, the qualitative exploration found that digital services can both enable access and be a barrier to access, and that patient priorities are often to navigate the system to access health care, making access a more important concept than DF to many. The third theme related to the impact of the COVID pandemic. Many practices responding to the practice survey reported increased digital service offerings and reduced provision of traditional forms of access. The exception to this was in relation to online appointment booking, where 44% of responding practices reported that they had offered this service pre-pandemic but did not do so at the time of the survey. Furthermore, in the qualitative exploration we found that the pandemic was associated with some initiatives being halted that have not subsequently resumed. Digital facilitation themes: The fourth theme related to how people define and identify DF. While, as a research team, we proposed a definition of digital facilitation, it is not yet a widely recognised concept and the qualitative exploration found that it was often difficult to have a working definition for DF given that it is movable and relative to a person’s circumstance. The fifth theme related to the types of DF. In our literature review, we found a focus on interventions that require practices to actively support patients to use digital services. This was in striking contrast with our practice survey where we found that the majority of practices reported passive and reactive modes of facilitation (e.g. 88% of practices used text messages or e-mails for DF and 91% provided ad hoc support to patients). The sixth theme relates to the differing foci of DF on initial sign-up versus supporting sustained use over time. The majority of research found in our review focused on initial sign-up. While in the patient survey we did find that registration was a substantial barrier (20% of responders to the patient survey cited not knowing how to register or finding registration too difficult as a reason for not using online services), the qualitative exploration found that supporting patients to register was often still reactive. Furthermore, although recognising that DF could go beyond initial sign-up, some practices felt that this was their only required contribution to the task of extending digital access. The seventh theme relates to who delivers facilitation. There was a mismatch between existing evidence identified in WP1, which suggested that general practitioners (GPs) and nurses undertake most facilitation, and our survey and qualitative findings that most facilitation efforts were conducted by receptionists and administrative staff. We also found a ‘bystander effect’, with patients, different staff groups and stakeholders all assuming that responsibility for DF lies elsewhere. The eighth and ninth themes related to the enablers and barriers of DF, respectively. Findings from our qualitative work were consistent with much of what emerged from the literature review. Enablers of DF include someone having specific responsibility for such efforts, with associated funding, time and other resources, platforms that enable easy registration and use, and a clear rationale for the digital services that can be understood by practice and patient (i.e. products that have a ‘good fit’ with what is needed). Barriers to effective facilitation include confusion about who is responsible for DF and why; practices using a variety of digital platforms; lack of consideration for the individual circumstances of patients; and assumptions being made about what people can and cannot do digitally based on stereotypes. In our patient survey, we found very low awareness of DF activities (apart from use of e-mail and text messages). Few (13%) responders to the patient survey reported being given help to use online services, but when that help was given, it was generally rated as useful. The 10th theme focuses on digital access and DF for patient subgroups. Age emerged as a common important dimension across the WPs. The literature review identified that older people may particularly benefit from direct, human support in accessing digital services. In the practice survey, most practices reported targeting older adults. However, in the patient survey we found that older patients were less likely to be aware of or make use of DF and were less likely to be told about or receive help to use digital services. In the qualitative work we found that the age of the individual is perceived to have an impact on both staff and patients’ digital knowledge, understanding, experience and confidence. Responders to the patient survey who were from ethnic minorities had long-term health conditions, did not speak English as a first language, or were in receipt of repeat prescriptions, were more likely to report awareness of and use of (passive) facilitation than other patients. But these groups were also less likely to be told about online services or to have received help to use them. The findings of our work focusing on patients living with mental health conditions were largely concordant with the findings of the main patient survey and qualitative research. There were some differences in the way that specific mental health conditions impacted on individuals’ contact with their practice, and consequently in the use by such individuals of digital services and in their need for DF. Responders in the patient survey mental health sample were more likely to report using digital services and to being aware of DF efforts than were responders to the main survey, but this was largely explained by differences in the sample demographics. The final theme considered the effectiveness of DF. There was no evidence around the cost effectiveness of DF, and the limited existing evidence on effectiveness almost entirely focused on initial sign-up of services. Reflecting this, our qualitative exploration found that some practices focused on the number of patients signed up to a service as evidence of the effectiveness of their facilitation efforts. Conclusions Digital facilitation is important in the context of the move to an NHS-enhanced digital opportunities and enhanced digital access in primary care service provision. Staff are spending time and effort to provide DF in general practices in England. Digital facilitation is viewed to have value and potential to increase the uptake of online services. Digital facilitation can take many forms, though most such efforts are reactive and passive. There is clear scope to develop a more proactive approach to facilitation that actively engages patients. There is currently a disconnect between the expectations and perceptions of what DF is happening and its potential effectiveness, and the reality seen in everyday practice. This is related to a lack of clarity over the responsibility for delivering DF and pressures on the time of general practice staff. Establishing clear lines of responsibility, and the development of digital tools and platforms that work for patients and practice staff, will both be needed, alongside investment in staff time and training, if DF is to deliver on the intended digital revolution. This project set out to explore DF that was already underway, with the potential of identifying good practice. However, we did not find an example of what might form a complete, practical intervention package. Future research should therefore focus on: co-development, involving patients and general practice staff, of DF, seeking to ensure a responsive and adaptive approach improving the presentation of practice websites for patient engagement with the intent of increasing uptake of digital tools and reducing the need for DF the best approaches to tailoring DF to different patient groups and identifying which patient groups are most likely to benefit from such efforts ensuring that the digital exclusion of certain groups, including, but not limited to, older patients, is investigated monitoring the sustained use of online services, not merely initial sign-up. Study registration This study is registered as ResearchRegistry6523 (www.researchregistry.com/browse-the-registry#home/?view_2_search=Di-Facto&view_2_page=1) and PROSPERO CRD42020189019 (www.crd.york.ac.uk/prospero/display_record.php?RecordID=189019). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128268) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 32. See the NIHR Funding and Awards website for further award information.

BackgroundSurvivorship care plans (SCPs) are provided at the completion of cancer treatment to aid in the transition from active treatment to long-term survivorship. They describe the details of a patient’s diagnosis and treatment and offer recommendations for follow-up appointments, referrals, and healthy behaviors. The plans are currently paper-based and become outdated as soon as a patient’s health status changes. There is a need to digitize these plans to improve their accessibility, modifiability, and longevity. With current technology, SCPs can be linked to mobile devices and activity trackers so that patients can track health behaviors and compare them to their clinical goals, taking charge of their own health. ObjectiveA mobile app, POSTHOC (POST-Treatment Health Outcomes of Cancer Survivors), that digitizes the SCP was developed, with goals of integrating it with wearable technologies and electronic medical records. Herein, we are conducting a randomized controlled trial that evaluates the POSTHOC app versus the traditional SCP on total symptom burden in the early posttreatment period. MethodsWe will recruit 54 patients who have recently completed curative therapy for cancer (any type) in person and remotely. They will be randomized 2:1, POSTHOC:usual care (unblinded). Those randomized to the POSTHOC group will receive their SCP via the app and will choose to focus on nutrition or exercise for the duration of the study based on their individual plan and personal preferences. Those randomized to the control group will get a paper-based plan. At baseline, 6 weeks, and 12 weeks, we will evaluate patient-reported outcomes, including total symptom burden (web-based questionnaire), diet (24-hour Automated Self-Administered [ASA24]), and physical activity (Fitbit Charge 6 [Google LLC]). We will also collect quantitative and qualitative feedback on the usability of the app from those in the POSTHOC arm to improve the app for future implementation studies, with a specific focus on patient-provider communication. For feasibility, we will calculate the percentage of patients who used the POSTHOC app at least 3 times per week. We will use linear mixed models to evaluate the effects of the POSTHOC app versus those of usual care on other outcomes at weeks 6 and 12. ResultsThis trial is open to accrual in the University of Maryland Medical System as of March 2024, and as of July 3, 2024, a total of 20 participants have consented. ConclusionsThis study is among the first to digitize the SCP in a mobile app and test the effects of a mobile health–delivered behavioral health intervention on symptom burden in cancer survivors. Our results will provide evidence about the effects of health self-management on symptoms. This knowledge will be integral to larger randomized controlled studies, integration with the electronic medical record, and nationwide implementation. Trial RegistrationClinicalTrials.gov NCT05499663; https://clinicaltrials.gov/ct2/show/NCT05499663 International Registered Report Identifier (IRRID)DERR1-10.2196/59222

Background: Patients with bone metastases from solid tumors often have additional treatment with bone targeted agents (BTAs) to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture leading toradiation therapy or surgery to the bone, spinal cord compression, or hypercalcemia. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown. Methods: Patients with bone metastases treated with immunotherapy within the Alpine Tumor Immunology Registry were compared based on whether they received an additional BTA such as denosumab or zoledronic acid. The primary endpoint was time to first SSE. Continuous data were summarized as median and range, categorical data using frequency counts and percentages. Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables. Results: One hundred and ninety-seven patients with bone metastases and treatment with immunotherapy such as nivolumab (48 %), pembrolizumab (40 %), atezolizumab (12 %), ipilimumab (9 %) and other immunotherapy (5 %) were included. The most frequent tumor types were lung cancer (50 %), malignant melanoma (11 %), renal cell cancer (10 %) and bladder cancer (9 %), respectively. One hundred and twenty-two patients (62 %) received a BTA treatment (91 % denosumab). The median treatment duration of a BTA was 178 days (min: 1 day, max: 2010 days). Out of the 197 patients, 47 (24 %) experienced at least one SSE, 100 (51 %) had bone pain. Ten of the 122 patients (8 %) receiving a BTA developed osteonecrosis of the jaw (ONJ). The percentage of patients without an SSE at fixed time points was higher if treated with a BTA (e.g., at 6 months, 92 % [95 % CI: 84 % - 96 %] versus 88 % [95 % CI: 77 % - 94 %]), but no significant difference in time to first SSE (HR 0.69; 95 % CI 0.34–1.39, log-rank p = 0.29) or time to first bone pain (HR: 0.85; 95 % CI: 0.51–1.43, p = 0.54) between these two groups could be detected. There were differences in OS between patients treated with a BTA and patients not treated with a BTA (HR: 1.46; 95 % CI: 1.01–2.10, p = 0.043). Conclusion: No significant difference in time to first SSE or bone pain was observed between patients who have received a BTA or not when treated with immunotherapy. Based on these retrospective results the indication of BTAs to reduce SSEs in cancer patients under treatment with immunotherapy needs further evaluation.

Diatoms are significant primary producers especially in cold, turbulent, and nutrient-rich surface oceans. Hence, they are abundant in polar oceans, but also underpin most of the polar food webs and related biogeochemical cycles. The cold-adapted pennate diatom Fragilariopsis cylindrus is considered a keystone species in polar oceans and sea ice because it can thrive under different environmental conditions if temperatures are low. In this perspective paper, we provide insights into the latest molecular work that has been done on F. cylindrus and discuss its role as a model alga to understand cold-adapted life.