On the crashworthiness analysis of bio-inspired DNA tubes.

This study presents a thorough numerical evaluation of the crashworthiness properties of a new bio-inspired DNA tubes (BIDNATs) with circular, elliptical, and rectangular cross-sections. Deformation and crashworthiness behaviors are evaluated using axial quasi-static crushing simulations by ABAQUS/Explicit (Abaqus 6.14, https://www.3ds.com/products-services/simulia/products/abaqus/ ). The study compares the performance of conventional tubes with rectangular and elliptical cross-sections to DNA-inspired tubes. Increasing the rotation angle leads to more helices and a pronounced helix angle, resulting in lower initial peak force (IPF). However, lower cross-section aspect ratios generally have higher IPF and specific energy absorption (SEA) values. BIDNATs with rectangular cross-sections and a 540° rotation angle have the lowest SEA and IPF values across all aspect ratios. Notably, for the 110/100 aspect ratio, the SEA of E110/100 is 71% higher than the conventional tube. Overall, BIDNATs with elliptical cross-sections and a 360° rotation angle exhibit higher SEA values and lower IPF values, particularly for a width (W) of 100 mm. Conventional circular and elliptical tubes generally have SEA values exceeding 6 J/g, with only E110/100 surpassing this among DNA-inspired tubes. The NE110/100 tube has the highest SEA, surpassing E110/100 by 54%, while its IPF is 10% greater than DNA-inspired E110/100. It's worth noting that conventional circular and elliptical tubes have higher IPF values compared to their DNA-inspired counterparts. These findings offer valuable insights for engineers and researchers in the design of crash tubes to improve overall vehicle safety for both occupants and pedestrians.

Elements of successful NIH grant applications.

Is there a formula for a competitive NIH grant application? The Serenity Prayer may provide one: "Grant me the serenity to accept the things I cannot change, the ability to change the things I can, and the wisdom to know the difference." But how to tell the difference? In this Perspective, we provide an inclusive roadmap-elements of NIH funding. Collectively, we have over 30 y of peer review experience as NIH Scientific Review Officers in addition to over 30 y of program experience as NIH Program Officers. This article distills our NIH experience. We use Euclid's 13-book landmark, The Elements, as our template to humbly share what we learned. We have three specific aims: inform, guide, and motivate prospective applicants. We also address ways that support diversity and inclusion among applicants and young investigators in biomedical research. The elements we describe come from a wide range of sources. Some themes will be general. Some will be specific. All will be candid. The ultimate goal is a competitive application, serenity, and hopefully both.

A Review of the Use of Native and Engineered Probiotics for Colorectal Cancer Therapy.

Colorectal cancer (CRC) is a serious global health concern, and researchers have been investigating different strategies to prevent, treat, or support conventional therapies for CRC. This review article comprehensively covers CRC therapy involving wild-type bacteria, including probiotics and oncolytic bacteria as well as genetically modified bacteria. Given the close relationship between CRC and the gut microbiota, it is crucial to compile and present a comprehensive overview of bacterial therapies used in the context of colorectal cancer. It is evident that the use of native and engineered probiotics for colorectal cancer therapy necessitates research focused on enhancing the therapeutic properties of probiotic strains.. Genetically engineered probiotics might be designed to produce particular molecules or to target cancer cells more effectively and cure CRC patients.

Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome.

Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.

Shaping research for people living with co-existing mental and physical health conditions: A research priority setting initiative from the United Kingdom.

INTRODUCTION: Those with severe and enduring mental ill health are at greater risk of long-term physical health conditions and have a reduced life expectancy as a result. Multiple factors compound this health inequality, and the need for setting research priorities in this area is highlighted with physical and mental healthcare services being separate, and limited multimorbidity research. METHODS: The aim of this exercise was to work in partnership with healthcare professionals and carers, family, friends and individuals with lived experience of both mental and physical health conditions, to set research priorities to help people with mental health conditions to look after their physical health. The exercise was guided by the James Lind Alliance approach. For this, a steering group was set up, two surveys were completed and a final priority workshop was conducted. RESULTS: This priority setting exercise guided by people's needs and lived experience has produced a set of well-defined research topics. Initially, 555 research questions were suggested in the first survey, which were refined to 54 questions for the second survey. A priority setting workshop was then conducted to get the final 10 priorities. CONCLUSIONS: Taking these topics forward to improve services and treatment for both mental and physical ill health may in turn improve physical health and lessen the reduced life expectancy of those living with mental ill health. PATIENT OR PUBLIC CONTRIBUTION: This work was completed in collaboration with people who have lived experience of mental ill health and physical health conditions, as well as carers, family and friends. Their contribution has been significant for this work from piloting surveys, amending language used and educating the researchers and contributing to this paper. The initial work was completed with a steering group and continued with surveys and workshops.

'It's Powerful' The impact of involving children and young people in developing paediatric research agendas: A qualitative interview study.

INTRODUCTION: There is a growing consensus that children and young people (CYP) should be involved in matters that concern them. Progress is made in involving CYP in developing pediatric research agendas (PRAs), although the impact of their involvement remains unknown. We aimed to evaluate the impact of involving CYP in developing PRAs and assess the extent to which postpatient and public involvement (post-PPI) activities were planned. METHODS: We conducted a qualitative study using in-depth interviews to identify and gain an in-depth understanding of the impact of involving CYP in developing PRAs. The transcripts were uploaded to Atlas.ti to be coded and organised. Dutch-language interviews were analysed and interpreted together with vocational education and training (VET) students. These students were aged between 14 and 18 years and were training to become nurses. RESULTS: Three CYP and 15 researchers decided to participate. We focused on three categories of impact: agenda-setting impact, individual impact and academic impact. Involving CYP creates a more enriched and clarified agenda. It ensured that both CYP and researchers underwent personal or professional growth and development, it created a connection between the people involved, awareness about the importance of involving CYP and it ensured that the people involved had a positive experience. The participants were unable to indicate the academic impact of their PRAs, but they did understand the key factors for creating it. In addition, the need to measure impact was highlighted, with a particular focus on assessing individual impact. DISCUSSION: Our study outlines the diverse subthemes of impact that arise from involving CYP in developing PRAs. Despite the potential of research agendas to amplify CYP voices, only a minority of researchers strategized post-PPI activities ensuring impactful outcomes, prompting the need for thorough evaluation of various impact forms and consistent alignment with the overarching goal of transforming the research field. PATIENT OR PUBLIC CONTRIBUTION: We involved VET students in the data analysis and interpretation phase by forming a young person advisory group. The data analysis of the interviews analysed by the VET students revealed four distinct themes: 1. Learnt new knowledge. 2. Learnt to collaborate. 3. Learnt to listen. 4. Assessment of the individual impact.

Job description and perception of clinical research personnel working in a network of French intensive care units.

BACKGROUND: There is a lack of information about the organisation and management of clinical research personnel in Europe and of their professional activity in intensive care. We therefore conducted a cross-sectional survey among personnel currently working in a French intensive care research network that involves 41 centres nationwide. The aim of the survey was to describe the personnel's personal and institutional organisation and management, their job perception in terms of satisfaction and stress, and suggestions for improvement. METHODS: Over 3 months in 2023, the research personnel received an electronic questionnaire on their personal and professional profile, past and present training, workplace and functions currently performed, personal knowledge about job skills required, job satisfaction and stress by as measured on a rating scale, and suggested ways of improvement. RESULTS: Ninety seven people replied to the questionnaire (a response rate of 71.3%), of whom 78 (57.3%) were sufficiently involved in intensive care to provide complete answers. This core sample had profiles in line with French recruitment policies and comprised mainly Bachelor/Master graduates, with nurses accounting for only 21.8%. The female to male ratio was 77:23%. Many responders declared to have a shared activity of technician (for investigation) and assistant (for quality control). More than 70% of the responders considered that most of the tasks required of each worker were major. Figures were much lower for project managers, who were few to take part in the survey. On a scale of 10, the median of job satisfaction was 7 for personal work organisation, 6 for training and for institutional organisation, and only 5 for personal career management. The median of job stress was 5 and was inversely correlated with satisfaction with career management. Respect of autonomy, work-sharing activity between investigation and quality control, a better career progression, financial reward for demanding tasks, and participation in unit staff meetings were the main suggestions to improve employee satisfaction. CONCLUSION: This nationwide survey provides a new insight into the activity of French clinical research personnel and points to ways to improve the quality and efficiency of this workforce.

Participatory methods used in the evaluation of medical devices: a comparison of focus groups, interviews, and a survey.

BACKGROUND: Stakeholder engagement in evaluation of medical devices is crucial for aligning devices with stakeholders' views, needs, and values. Methods for these engagements have however not been compared to analyse their relative merits for medical device evaluation. Therefore, we systematically compared these three methods in terms of themes, interaction, and time-investment. METHODS: We compared focus groups, interviews, and an online survey in a case-study on minimally invasive endoscopy-guided surgery for patients with intracerebral haemorrhage. The focus groups and interviews featured two rounds, one explorative focussing on individual perspectives, and one interactive focussing on the exchange of perspectives between participants. The comparison between methods was made in terms of number and content of themes, how participants interact, and hours invested by all researchers. RESULTS: The focus groups generated 34 themes, the interviews 58, and the survey 42. Various improvements for the assessment of the surgical procedure were only discussed in the interviews. In focus groups, participants were inclined to emphasise agreement and support, whereas the interviews consisted of questions and answers. The total time investment for researchers of focus groups was 95 h, of interviews 315 h, and survey 81 h. CONCLUSIONS: Within the context of medical device evaluation, interviews appeared to be the most appropriate method for understanding stakeholder views since they provide a scope and depth of information that is not generated by other methods. Focus groups were useful to rapidly bring views together. Surveys enabled a quick exploration. Researchers should account for these methodological differences and select the method that is suitable for their research aim.

Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials. RESULTS: This qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had an IDS variant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with large IDS deletions; 67% of these patients were rated as improved/improving or stabilized disease. CONCLUSIONS: This qualitative analysis provides a snapshot of clinicians' considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.

Ending "domestic helicopter research".

"Helicopter research" refers to a practice where researchers from wealthier countries conduct studies in lower-income countries with little involvement of local researchers or community members. This practice also occurs domestically. In this Commentary, we outline strategies to curb domestic helicopter research and to foster equity-centered collaborations.

Exploring stem cell frontiers: definitions, challenges, and perspectives for regenerative medicine.

Each year, the European Summer School on Stem Cell Biology and Regenerative Medicine (SCSS) attracts early-career researchers and actively practicing clinicians who specialise in stem cell and regenerative biology. The 16th edition of this influential course took place from 12th to 19th September 2023 on the charming Greek island of Spetses. Focusing on important concepts and recent advances in stem cells, the distinguished faculty included experts spanning the spectrum from fundamental research to clinical trials to market-approved therapies. Alongside an academically intensive programme that bridges the various contexts of stem cell research, delegates were encouraged to critically address relevant questions in stem cell biology and medicine, including broader societal implications. Here, we present a comprehensive overview and key highlights from the SCSS 2023.