Impact of COVID-19 on longitudinal breast cancer research studies involving TNBC patients

Background Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancer diagnoses but is linked to worse outcomes and comprises a disproportionate number of breast cancer deaths. The TNBC pilot study is a prospective longitudinal study to provide a critical resource for understanding TNBC disease. However, the pandemic impacted the collection of samples. Objective To highlight the impacts of COVID-19 on this longitudinal cancer translational research study including the patient's perspective and to develop recommendations to avoid future disruptions. Methods 389 participants were enrolled in the prospective longitudinal cohort, which collected serial blood samples for up to 5 years. Due to the pandemic, research was curtailed for 6 months due to concerns about patient safety, halting the collection of blood samples. Missed samples and data gaps were documented. To complement this, we initiated a survey capturing the patient perspective on their experience of the study disruption due to COVID. Results 217 enrolled participants missed a blood draw or had a collection outside the study window. 158 patients missed 1 time-point collection, and 59 patients missed >= 2 collections. Of the 217 participants who missed a collection, 6 disease recurrence diagnoses and 3 deaths occurred during research curtailment. The collection of survey responses from participants is ongoing and will be presented at the AACR Annual Meeting. Conclusion Missed samples resulted in irreplaceable data gaps critical to monitoring patient outcomes, and reduced cohort sampling during the pandemic. Our current knowledge of the risks suggests that with proper informed consent, collections could have continued. To mitigate disruption in future clinical studies, clear plans should be part of study design to provide continuity. The participants' experience to be reported will also help researchers understand their issues and help develop policies. (Table Presented).

Ultra-high field cardiac MRI in large animals and humans for translational cardiovascular research.

A key step in translational cardiovascular research is the use of large animal models to better understand normal and abnormal physiology, to test drugs or interventions, or to perform studies which would be considered unethical in human subjects. Ultrahigh field magnetic resonance imaging (UHF-MRI) at 7 T field strength is becoming increasingly available for imaging of the heart and, when compared to clinically established field strengths, promises better image quality and image information content, more precise functional analysis, potentially new image contrasts, and as all in-vivo imaging techniques, a reduction of the number of animals per study because of the possibility to scan every animal repeatedly. We present here a solution to the dual use problem of whole-body UHF-MRI systems, which are typically installed in clinical environments, to both UHF-MRI in large animals and humans. Moreover, we provide evidence that in such a research infrastructure UHF-MRI, and ideally combined with a standard small-bore UHF-MRI system, can contribute to a variety of spatial scales in translational cardiovascular research: from cardiac organoids, Zebra fish and rodent hearts to large animal models such as pigs and humans. We present pilot data from serial CINE, late gadolinium enhancement, and susceptibility weighted UHF-MRI in a myocardial infarction model over eight weeks. In 14 pigs which were delivered from a breeding facility in a national SARS-CoV-2 hotspot, we found no infection in the incoming pigs. Human scanning using CINE and phase contrast flow measurements provided good image quality of the left and right ventricle. Agreement of functional analysis between CINE and phase contrast MRI was excellent. MRI in arrested hearts or excised vascular tissue for MRI-based histologic imaging, structural imaging of myofiber and vascular smooth muscle cell architecture using high-resolution diffusion tensor imaging, and UHF-MRI for monitoring free radicals as a surrogate for MRI of reactive oxygen species in studies of oxidative stress are demonstrated. We conclude that UHF-MRI has the potential to become an important precision imaging modality in translational cardiovascular research.

Development of a clinical and translational research curriculum for undergraduate students.

Introduction: Research participation during undergraduate years has a powerful influence on career selection and attitudes toward scientific research. Most undergraduate research programs in academic health centers are oriented toward basic research or address a particular disease focus or research discipline. Undergraduate research programs that expose students to clinical and translational research may alter student perceptions about research and influence career selection. Methods: We developed an undergraduate summer research curriculum, anchored upon a clinical and translational research study developed to address a common unmet needs in neonatal nurseries (e.g., assessment of neonatal opioid withdrawal syndrome). Program topics reflected the cross-disciplinary expertise that contributed to the development of this "bedside to bench" study, including opioid addiction, vulnerable populations, research ethics, statistics, data collection and management, assay development, analytical laboratory analysis, and pharmacokinetics. The curriculum was delivered through three offerings over 12 months, using Zoom video-conferencing due to restrictions imposed by the COVID-19 pandemic. Results: Nine students participated in the program. Two-thirds reported the course enhanced their understanding of clinical and translational research. Over three-quarters reported the curriculum topics were very good or excellent. In open-ended questions, students reported that the cross-disciplinary nature of the curriculum was the strongest aspect of the program. Conclusion: The curriculum could be readily adapted by other Clinical and Translational Science Award programs seeking to provide clinical and translational research-oriented programs to undergraduate students. Application of cross-disciplinary research approaches to a specific clinical and translational research question provides students with relevant examples of translational research and translational science.

Anthropause and Human Behaviour: Contributions from a Situated Educational Neuroscience

Objective: We develop a theoretical discussion from our perspective of the situated educational neuroscience, based on the relational anthropology point of view, to generate ambits of discussion in which the educational neuroscience can contribute into the context of COVID-19 pandemic and pospandemic. Subject: The context of the COVID-19 pandemic has made it possible to put in tension issues that were pending on the global agenda. Among these issues, the importance of the human being as part of the ecosystem with which they maintain co-construction relationships is not minor. Situated educational neuroscience is a tool that can bring valuable contributions to the discussion to collaborate in addressing this tension. Development: We organize de argumentation in four sections: 1. The opportunity the anthropause posts to the humankind and its relations with their environment, 2. The role that studies on behaviour and evolution have on this opportunity, 3. The contribution of a situated educational neuroscience as a framework and transdiscipline which works on translational research in this context of pandemics and anthropause, and 4. The succinct presentation of two examples where we argue that a situated educational neuroscience has tools to contribute. Conclusions: We propose conclusions open to discussion where we return to the idea of a situated educational neuroscience which is committed with its context. As an approach or as a transdiscipline with translational research functions, we consider that a situated educational neuroscience contains tools that can contribute to the conversation with other sciences and disciplines and with the empirical knowledge of communities, in order to join efforts to overcome social injustices and move forward as humankind from this current pandemic situa- tion, having acquired strategies of resilience that can serve to deal with other persistent and future situations.

The evolving regulatory landscape in regenerative medicine.

Regenerative medicine as a field has emerged as a new component of modern medicine and medical research that encompasses a wide range of products including cellular and acellular therapies. As this new field emerged, regulatory agencies like the Food and Drug Administration (FDA) rapidly adapted existing regulatory frameworks to address the transplantation, gene therapy, cell-based therapeutics, and acellular biologics that fall under the broader regenerative medicine umbrella. Where it has not been possible to modify existing regulation and processes, entirely new frameworks have been generated with the intention of providing flexible, forward-facing systems to regulate this rapidly growing field. This review discusses the current state of FDA regulatory affairs in the context of stem cells and extracellular vesicles by highlighting gaps in the current regulatory system and then discussing where regulatory science in regenerative medicine may be headed based on these gaps and the FDA's historical ability to deal with emerging fields. Lastly, we utilize case studies in stem cell and acellular based treatments to demonstrate how regulatory science has evolved in regenerative medicine and highlight the ongoing clinical efforts and challenges of these therapies.

Resilience: Biological Basis and Clinical Significance - A Perspective Report from the International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force.

The Resilience is a construct receiving growing attention from the scientific community in geriatrics and gerontology. Older adults show extremely heterogeneous (and often unpredictable) responses to stressors. Such heterogeneity can (at least partly) be explained by differences in resilience (i.e., the capacity of the organism to cope with stressors). The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met in Boston (MA,USA) on April 20, 2022 to discuss the biological and clinical significance of resilience in older adults. The identification of persons with low resilience and the prompt intervention in this at-risk population may be critical to develop and implement preventive strategies against adverse events. Unfortunately, to date, it is still challenging to capture resilience, especially due to its dynamic nature encompassing biological, clinical, subjective, and socioeconomic factors. Opportunities to dynamically measure resilience were discussed during the ICFSR Task Force meeting, emphasizing potential biomarkers and areas of intervention. This article reports the results of the meeting and may serve to support future actions in the field.

Proceedings of the 6th National Patient Reported Outcome Measures (PROMs) Annual Conference

The proceedings contain 47 papers. The topics discussed include: long COVID rehabilitation services, Cardiff and Vale and Cwm Taf Morgannwg University health boards: social return on investment;the clinical meaning of family reported outcome measure (FROM-16) scores: translational research to support holistic clinical practice;patient-centered outcome measure design: the perspectives and preferences of children and young people with life-limiting or life-threatening conditions;co-creation of a patient reported outcome measure for older people with frailty and acute care needs (PROM-OPAC);PROMs: coming of age in lymphoedema services in Wales;ForMi-person-centered planning and outcomes recording app;true colors online mood monitoring in the bipolar disorder research network (BDRN) research program: challenges, benefits and importance of personalization;patient reported outcome measures for rheumatoid arthritis disease activity: using Rasch measurement theory to achieve more meaningful measurement;developing a roadmap towards national collection of electronic patient-reported outcomes for people with chronic kidney disease in the UK;and measuring bereavement support needs in people bereaved during Covid-19;the adaptation and development of a bereavement support needs scale.

Are researchers in academic medicine flourishing? A survey of midcareer Ph.D. and physician investigators.

Introduction: Midcareer research faculty are a vital part of the advancement of science in U.S. medical schools, but there are troubling trends in recruitment, retention, and burnout rates. Methods: The primary sampling frame for this online survey was recipients of a single R01 or equivalent and/or K-award from 2013 to 2019. Inclusion criteria were 3-14 years at a U.S. medical school and rank of associate professor or two or more years as assistant professor. Forty physician investigators and Ph.D. scientists volunteered for a faculty development program, and 106 were propensity-matched controls. Survey items covered self-efficacy in career, research, work-life; vitality/burnout; relationships, inclusion, trust; diversity; and intention to leave academic medicine. Results: The majority (52%) reported receiving poor mentoring; 40% experienced high burnout and 41% low vitality, which, in turn, predicted leaving intention (P < 0.0005). Women were more likely to report high burnout (P = 0.01) and low self-efficacy managing work and personal life (P = 0.01) and to be seriously considering leaving academic medicine than men (P = 0.003). Mentoring quality (P < 0.0005) and poor relationships, inclusion, and trust (P < 0.0005) predicted leaving intention. Non-underrepresented men were very likely to report low identity self-awareness (65%) and valuing differences (24%) versus underrepresented men (25% and 0%; P < 0.0005). Ph.D.s had lower career advancement self-efficacy than M.D.s (P < .0005). Conclusions: Midcareer Ph.D. and physician investigators faced significant career challenges. Experiences diverged by underrepresentation, gender, and degree. Poor quality mentoring was an issue for most. Effective mentoring could address the concerns of this vital component of the biomedical workforce.

Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.

Introduction: Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of "informativeness," highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise. Methods and Results: Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies. Conclusions: We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.

Translational research strategies

Advances in basic research have generated a better understanding of the mechanisms in human diseases;however, only a small part of the scientific discoveries have generated new treatments, changes in clinical practice and new diagnostic methods. Trying to find faster implementation solutions, the Translational technique "from bench to bedside” offers the advantage of establishing a continuous and two-way communication path to transmit and make known data acquired from the laboratory, in basic molecular and genetic research, through animal experiments, to the clinical aspects of acceptance and treatment in humans. It is key that basic research provides knowledge that responds to the needs of clinical practice. An example is the rapid development of treatments in the COVID-19 pandemic. In this chapter of the book, we make reference to specific areas in which translational research is being used and should be encouraged to develop newer and more effective therapies for substance use disorder. Multiple tools from basic research are already opening up in the modern medicine of addictive disorders. With the development of neurobiology and a better understanding of the brain, we now know that addiction is a disease that affects both the brain and behavior. Basic and clinical research on addictive disorders focuses on understanding the molecular bases of addiction, on the genetic and epigenetic variations involved in the long-term persistence of addiction, and on the study of new pharmacological targets with therapeutic potential. A future line of work is the complete analysis of the individual's genome, which would make it possible to detect small DNA variations called single nucleotide polymorphisms. Finally, in this chapter we wanted to know the current lines of research that can make health service providers better equipped to provide patients with the most appropriate treatments and dosages of medications for addiction. © 2023 Elsevier Inc. All rights reserved.

The Importance of Animal Models in Biomedical Research: Current Insights and Applications.

Animal research is considered a key element in advance of biomedical science. Although its use is controversial and raises ethical challenges, the contribution of animal models in medicine is essential for understanding the physiopathology and novel treatment alternatives for several animal and human diseases. Current pandemics' pathology, such as the 2019 Coronavirus disease, has been studied in primate, rodent, and porcine models to recognize infection routes and develop therapeutic protocols. Worldwide issues such as diabetes, obesity, neurological disorders, pain, rehabilitation medicine, and surgical techniques require studying the process in different animal species before testing them on humans. Due to their relevance, this article aims to discuss the importance of animal models in diverse lines of biomedical research by analyzing the contributions of the various species utilized in science over the past five years about key topics concerning human and animal health.

Microbiome in the Framework of Predictive, Preventive and Personalised Medicine

The human body is inhabited by trillions of diverse microorganisms collectively called "microbiome" or "microbiota". Microbiota consists of bacteria, viruses, fungi, protozoa, and archaea. Microbiome demonstrates multi-faceted effects on human physical and mental health. Per evidence there is a multi-functional interplay between the whole-body microbiome composition on the epithelial surfaces including skin, nasal and oral cavities, airway, gastro-intestinal and urogenital tracts on one hand and on the other hand, the individual health status. Microbiota composition as well as an option to modulate it - together create a highly attractive operation area for the translational bio/medical research with multi-professional expertise and healthcare-relevant output in the framework of predictive, preventive and personalised medicine (PPPM/3 PM). Advanced PPPM strategies implemented in the microbiome area are expected to significantly improve individual outcomes and overall cost-efficacy of healthcare. According to the accumulated research data, corresponding diagnostic and treatment approaches are applicable to primary care (health risk assessment in individuals with sub-optimal health conditions and prevention of a disease development), secondary care (personalised treatment of clinically manifested disorders preventing a disease progression) and tertiary care (making palliation to an optimal management of non-curable diseases). In the current book, we do highlight the implementation potential of the microbiome-relevant research in the framework of predictive diagnostics, targeted prevention and treatments tailored to the individualised patient profile.Copyright © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Czech Cardiovascular Research and Innovation Day 2022

The proceedings contain 67 papers. The topics discussed include: role of endomyocardial biopsy in differential diagnosis of non- -ischemic cardiomyopathy;metformin treatment is associated with improved quality of life and outcome in patients with diabetes and advanced heart failure (HFREF);translational research in the field of inherited arrhythmias;same day discharge via a dedicated radial lounge - results of 1-year experience during the COVID-19 pandemic;functional assessment of microcirculation in takotsubo cardiomyopathy - a pilot study;an interplay of genetics and inflammation affecting left ventricular reverse remodeling in dilated cardiomyopathy;sildenafil inhibits pulmonary hypertension induced by left heart pressure overload in rats;predicting long-term survival after an ischemic stroke;and longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in the Czech population. are there any sex differences?.

Effectiveness and co-benefits of a telephone-based intervention in reducing obesity risk of children aged 2-4 years: findings from a pragmatic randomised controlled trial during the COVID-19 pandemic in Australia

Background: Evidence of effective early childhood obesity prevention is scarce and mainly derived from face-to-face interventions. However, the COVID-19 pandemic drastically reduced face-to-face health programmes globally. This study assessed effectiveness of a telephone-based intervention in reducing obesity risk of young children. Method(s): We adapted a study protocol (developed before the pandemic) and conducted a pragmatic randomised controlled trial of 662 women with children aged 2 years (mean age 24.06 months [SD 0.69]) during March, 2019, and October, 2021, extending the original planned intervention of 12 months to 24 months. The adapted intervention comprised five telephone-based support sessions plus text messages over a 24-month period (at child ages 24-26 months, 28-30 months, 32-34 months, 36-38 months, and 42-44 months). The intervention group (n=331) received staged telephone plus SMS support regarding healthy eating, physical activity, and information about COVID-19. The control group (n=331) received four staged mail-outs on information not related to the obesity prevention intervention, such as toilet training, language development, and sibling relationships, as a retention strategy. The intervention effects on BMI (primary outcome) and eating habits (secondary outcome), and perceived co-benefits, were evaluated using surveys and qualitative telephone interviews at 12 months and 24 months after baseline (age 2 years). The trial is registered with the Australian Clinical Trial Registry, ACTRN12618001571268. Finding(s): Of 662 mothers, 537 (81%) completed the follow-up assessments at 3 years, and 491 (74%) completed the follow-up assessment at 4 years. Multiple imputation analysis showed no significant difference in mean BMI between the groups. Among low-income families (ie, annual household income <AU$80 000) at age 3 years, the intervention was significantly associated with a lower mean BMI (16.26 kg/m2 [SD 2.22]) in the intervention group than in the control group (16.84 kg/m2 [2.37];p=0.040), a difference of -0.59 (95% CI -1.15 to -0.03;p=0.040). Children in the intervention group were more likely not to eat in front of the television than the control group, with an adjusted odds ratio (aOR) of 2.00 (95% CI 1.33 to 2.99) at 3 years and an aOR of 2.50 (1.63 to 3.83) at 4 years. Qualitative interviews with 28 mothers revealed that the intervention increased their awareness, confidence, and motivation to implement healthy feeding practices, particularly for families from culturally diverse backgrounds (ie, speaking a language other than English at home). Interpretation(s): A telephone-based intervention was well received by the mothers who participated in the study. The intervention could reduce children's BMI from low-income families. Telephone-based support targeted at low-income families and families from culturally diverse backgrounds could reduce current inequalities in childhood obesity. Funding(s): The trial was funded under the NSW Health Translational Research Grant Scheme 2016 (number TRGS 200) and also by a National Health and Medical Research Council Partnership grant (number 1169823).Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

An ontology for very large numbers of longitudinal health records to facilitate data mining and machine learning

Despite the extensive experience of the authors working in industry with a variety of electronic health records that worked well in their intended context, none currently available in reasonably large numbers seem to have ontologies and formats that will scale well to very large numbers of detailed cradle-to-grave longitudinal health records facilitating knowledge extraction. By that we mean data mining, Deep Learning neural nets and all related analytic and predictive methods for biomedical research and clinical decision support potentially applied to the health records of an entire nation. They are mostly far too complicated to support frequent high-dimensional analysis, which is required because such records will update (or should update) dynamically on a regular basis, will in future include new tests etc. acquired daily by translational medical research, and not least allow public health, research, and diagnostic, vaccine, and drug development teams to respond quickly to emergent epidemics like COVID-19. A Presidential Advisory team call in 2010 for interoperability and ease of data mining for medical records is discussed and the situation seems still not fully resolved. The solution appears to lie between efficient comma separated value files and the ability to embellish these with a moderate degree of more elaborate ontology. One recommendation is made here with discussion and analysis that should guide alternative and future approaches. It combines demographic, comorbidity, genomic, diagnostic, interventional, and outcomes information along with time/date stamping method appropriate to analysis, with facilities for special research studies. By using a "metadata operator", a suitable balance between a comma separated values file and an ontological structure is possible.Copyright © 2023 The Authors

Lessons Learned and Future Actions: Modifying a Stroke Specific Self-Management Program.

Background: Self-management programs have been shown to be effective at providing support to individuals who want to manage chronic health conditions independently. It has been shown that adapting self-management programs for different diagnostic groups, such as stroke, is essential. Objective: To report modifications made during trial implementation, the barriers identified during the delivery of an evidence based, stroke-specific self-management program and minor data (including strategies made) from a small cohort of stroke survivors with multiple chronic conditions. Methods: Prospective type III hybrid implementation-effectiveness trial for stroke survivors, with chronic conditions, living in the community, and interested in self-management. Modifications were reported by the following: (1) researcher reflections (2) barriers to implementation and (3) strategies used to address the barrier using the Consolidated Framework for Implementation Research (CFIR) guidelines from field notes. Results: Twenty-five individuals consented (42% of eligible sample) at the time of acute stroke and five were interested in continuing at the 3-month call. Multiple barriers to implementation were identified, resulting in modifications. For example, before the group sessions began, the COVID-19 pandemic necessitated changes to the intervention delivery. The protocol was modified to an online mode of delivery. In total, there were seven modifications made. Conclusions: The CFIR was a facilitative tool to report barriers and strategies and emphasized the importance of comprehensive reporting. The modifications to the study were an essential first step to address the research climate and needs of this stroke cohort. Next steps include continued research with a larger cohort to implement effective strategies and answer the clinical question of effectiveness of the adapted and modified intervention.

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for Translational Research.

The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality.

Neutralization against Omicron variant in transplant recipients after three doses of mRNA vaccine.

The SARS-CoV-2 virus Omicron variant has now supplanted wild-type virus as the dominant circulating strain globally. Three doses of mRNA COVID-19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron-specific neutralization in transplant recipients after three-doses of mRNA-1273 vaccine. Neutralization was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney-pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA-1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log10 ID50 of 2.38 [range 1.34-3.57]). At 3 months, 8/51 (15.7%) were positive (median log10 ID50 [1.68; range 1.12-3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild-type, and Omicron vs. Delta (p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti-RBD response still had undetectable Omicron-specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients.