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Objectives To compare, in a retrospective study, pathological specimens of prostate cancer detected in additional areas of a 12‐core biopsy with tumours detected using traditional sextant biopsy. Patients and methods The study included 27 patients who had undergone radical prostatectomy (RP) for prostate cancer. Prostatectomy specimens of cancers detected using standard sextant biopsies were compared with those detected using six additional core biopsies. The RP specimens were analysed for cancer volume, Gleason score, tumour grade (Mostofi) and pathological stage. Results Of the 27 patients, six (29%) had cancer detected in the extra six biopsy cores which would have otherwise have been undetected using sextant biopsy. Only two insignificant cancers were detected. The mean Gleason score was 6.1 for cancer detected by the sextant or 12‐core method (P = 0.907); the mean grade (Mostofi) was 2.1 and 2.33, respectively (P = 0.29). The final tumour stage in the 21 patients undergoing sextant biopsy was pT2 in 13 and pT3 in eight, compared with six pT2 tumours in the six patients diagnosed using extra biopsies. The mean (median, range) tumour volume was 5.7 (3.5, 0.312–23.75) mL for cancers detected on sextant biopsy and 1.99 (1.85, 0.4–3.6) mL in the six cancers detected using extra cores (P = 0.0138). Conclusion The detection of prostate cancer was increased using extra biopsy cores. There was a significant difference in tumour volume but not in Gleason score, Mostofi grade or final pathological tumour stage between tumours diagnosed using 12 cores and those detected on sextant biopsy. [ABSTRACT FROM AUTHOR]

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates. Through rational mutagenesis and screening, TDO variants with substantially improved activity over the wild-type enzyme were identified. Homology modeling, docking studies, molecular dynamics simulations, and substrate tunnel analysis were applied in an effort to elucidate how the identified mutations resulted in improved activity for this polar substrate class. These analyses revealed modification of the substrate tunnel as the likely cause of the improved activity observed with the best-performing enzyme variants., (© 2024 Wiley Periodicals LLC.)

This autoethnography describes an illness episode caused by breastfeeding complications. It focuses on informed consent processes accompanying this illness episode. Informed consent is a cornerstone of ethical medical practice and has to be obtained before a medical intervention can legally be implemented. It is therefore not trivial that in practice, informed consent processes often fail to achieve what they are set out to. With this autoethnography, I want to provide a review of how informed consent processes can fail in the context of breastfeeding, but also draw attention to what these situations can mean and feel like for those affected. I provide in-depth descriptions of five scenes from my illness episode each representing a different barrier to informed consent. The scenes were developed based on emotional recall and written to grant access to the emotional dimensions of my experience in the tradition of evocative autoethnography. As part of my story, I engage with various issues like practices of prescribing, communicative requirements in vulnerable situations to ensure understanding, the dual purpose of informed consent in the moral and legal realm, and the moralized breastfeeding discourse. Possible routes for change to abolish or reduce described barriers to informed consent are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Central nervous system lymphomas (CNSL) display remarkable clinical heterogeneity, yet accurate prediction of outcomes remains challenging. The IPCG criteria are widely used in routine practice for the assessment of treatment response. However, the value of the IPCG criteria for ultimate outcome prediction is largely unclear, mainly due to the uncertainty in delineating complete from partial responses during and after treatment., Methods: We explored various MRI features including semi-automated 3D tumor volume measurements at different disease milestones and their association with survival in 93 CNSL patients undergoing curative-intent treatment., Results: At diagnosis, patients with more than 3 lymphoma lesions, periventricular involvement, and high 3D tumor volumes showed significantly unfavorable PFS and OS. At first interim MRI during treatment, the IPCG criteria failed to discriminate outcomes in responding patients. Therefore, we randomized these patients into training and validation cohorts to investigate whether 3D tumor volumetry could improve outcome prediction. We identified a 3D tumor volume reduction of ≥97% as the optimal threshold for risk stratification (=3D early response, 3D_ER). Applied to the validation cohort, patients achieving 3D_ER had significantly superior outcomes. In multivariate analyses, 3D_ER was independently prognostic of PFS and OS. Finally, we leveraged prognostic information from 3D MRI features and circulating biomarkers to build a composite metric that further improved outcome prediction in CNSL., Conclusions: We developed semi-automated 3D tumor volume measurements as strong and independent early predictors of clinical outcomes in CNSL patients. These radiologic features could help improve risk stratification and help guide future treatment approaches., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biobanks are important infrastructures facilitating biomedical research. After a decade of rolling out such infrastructures, a shift in attention to the sustainability of biobanks could be observed in recent years. In this regard, an increase in the as yet relatively low utilisation rates of biobanks has been formulated as a goal. Higher utilisation rates can only be achieved if the perspectives of potential users of biobanks-particularly researchers not yet collaborating with biobanks-are adequately considered. To better understand their perspectives, a survey was conducted at ten different research institutions in Germany hosting a centralised biobank. The survey targeted potential users of biobank services, i.e. researchers working with biosamples. It addressed the general demand for biosamples, strategies for biosample acquisition/storage and reasons for/against collaborating with biobanks. In total, 354 researchers filled out the survey. Most interestingly, only a minority of researchers (12%) acquired their biosamples via biobanks. Of the respondents not collaborating with biobanks on sample acquisition, around half were not aware of the (services of the) respective local biobank. Those who actively decided against acquiring biosamples via a biobank provided different reasons. Most commonly, respondents stated that the biosamples required were not available, the costs were too high and information about the available biosamples was not readily accessible. Biobanks can draw many lessons from the results of the survey. Particularly, external communication and outreach should be improved. Additionally, biobanks might have to reassess whether their particular collection strategies are adequately aligned with local researchers' needs., (© 2021. The Author(s).)

Boredom has been identified as one of the greatest psychological challenges when staying at home during quarantine and isolation. However, this does not mean that the situation necessarily causes boredom. On the basis of 13 explorative interviews with bored and non-bored persons who have been under quarantine or in isolation, we explain why boredom is related to a subjective interpretation process rather than being a direct consequence of the objective situation. Specifically, we show that participants vary significantly in their interpretations of staying at home and, thus, also in their experience of boredom. While the non-bored participants interpret the situation as a relief or as irrelevant, the bored participants interpret it as a major restriction that only some are able to cope with.

This article will employ a database from a large hospice provider with offices in 16 states to examine the impact of religious preference on hospice choice. Little work has been done on this issue, even though religion is the only social institution that specifically addresses the end of life. Hospice work, in particular, has drawn little attention despite it effecting millions of patients and their families. Of all the medical subspecialties, hospice is one of the most effected by society's views on death and religious views of dying. It is also the only government-funded medical service that requires religious support be made available to patients. Our hypothesis is that certain religious groups have a predisposition against end-of-life interventions and will be less likely to utilize hospice. This impacts a multibillion dollar a year industry that supplies hospice service to millions of patients, and our research points to one major religious group not accessing their hospice benefit at the same rate as other denominations.

Background: The German Biobank Node (GBN) is the central hub for German biobank activities and coordinates the German Biobank Alliance (GBA) to which 11 biobank sites in Germany belong. GBN, in cooperation with designated members of GBA, has developed various services and products for the German biobank community. To ensure that services and products are well aligned with the needs and interests of relevant stakeholders, GBN actively engages with its diverse stakeholder groups through different methods. Important stakeholder groups are the members of GBA who are generally the first users of developed products and services. Methods and Materials: Members of GBA were surveyed anonymously through a web-based application. The survey was sent to all members registered with an internal communication platform. Participants were primarily asked about their experiences with GBN, developed products and services, their wishes for the future of GBN/GBA, and their attitudes toward intensified cooperation on the European level. Answers were analyzed using descriptive statistics and qualitative content analysis. Results: Overall 63 of 110 registered GBA members (response rate of 57%) finished the survey. Participants were overall satisfied with the work of GBN and developed products and services. They also pointed out room for improvement. Participants, for example, proposed to shorten the survey developed for biobanks to engage with their users. They also shared what additional support wishes they had, for example, uniform cost models or use and access policies for the GBA community. Discussion: The survey was helpful to get a good overview of the experiences and attitudes of GBA members before making services and products available to other actors in the German biobank community. GBN will use the feedback to improve its work and to guide future strategy development. Survey research has shown an adequate method to engage with this particular stakeholder group, but further research on choosing methods for stakeholder engagement might be helpful.

Public health institutions increasingly realize the importance of creating a culture in their organizations that values ethics. When developing strategies to strengthen ethics, institutions will have to take into account that while public health research projects typically undergo thorough ethics review, activities considered public health practice may not be subjected to similar oversight. This approach, based on a research-practice dichotomy, is increasingly being criticized as it does not adequately identify and manage ethically relevant risks to those affected by nonresearch activities. As a reaction, 3 major public health institutions (the World Health Organization, US Centers for Disease Control and Prevention, and Public Health Ontario) have implemented mechanisms for ethics review of public health practice activities. In this article, we describe and critically discuss the different modalities of the 3 approaches. We argue that although further evaluation is necessary to determine the effectiveness of the different approaches, public health institutions should strive to implement procedures to ensure that public health practice adheres to the highest ethical standards.

Aberrant expression of the transcription factor double homeobox protein 4 (DUX4) can lead to a number of diseases including facio-scapulo-humeral muscular dystrophy (FSHD), acute lymphoblastic leukemia, and sarcomas. Inhibition of DUX4 may represent a therapeutic strategy for these diseases. By applying Systematic Evolution of Ligands by EXponential Enrichment (SELEX), we identified aptamers against DUX4 with specific secondary structural elements conveying high affinity to DUX4 as assessed by fluorescence resonance energy transfer and fluorescence polarization techniques. Sequences analysis of these aptamers revealed the presence of two consensus DUX4 motifs in a reverse complementary fashion forming hairpins interspersed with bulge loops at distinct positions that enlarged the binding surface with the DUX4 protein, as determined by crystal structure analysis. We demonstrate that insertion of specific structural elements into transcription factor binding oligonucleotides can enhance specificity and affinity., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.)

Increasingly, researchers are required to engage stakeholders in health-related research projects. "Stakeholder" in this context are those people who may be directly or indirectly affected by the planned research or the research object. This could be, for example, patients, relatives, and health personnel, but also political decision-makers. Those conducting stakeholder engagement are faced with many open questions like what activities are meant by engagement, for what purpose researchers should engage stakeholders, who should be involved, or how best to design engagement activities.From 28 to 29 March 2019 the interdisciplinary conference "Consulting or Engaging? The Role of Stakeholders in Health Research" took place at LMU Munich. The aim of the conference was to facilitate cross-disciplinary discourse on research engagement of various stakeholder groups. Different application contexts were examined, such as public health research, clinical research, health services research, and bioethical deliberation.This conference report structures and explains the main topics discussed during the conference from the perspective of the organizers. It thereby addresses the question of inclusivity and exclusivity of frequently used terms for stakeholder engagement, reflects on different strategies for justifying stakeholder engagement, and provides an overview of different approaches to stakeholder engagement as well as of methodological and practical challenges in implementing engagement activities.

Under the umbrella of the German Biobank Node (GBN), 11 biobanks and two IT development centers are funded by the Federal Ministry of Education and Research (BMBF) to work together in the German Biobank Alliance (GBA). Their common aim is to make existing biomaterials hosted by different biobanks nationally and internationally available for biomedical research. This position article reflects and summarizes contributions and comments made during a GBA workshop, on the cooperation between academic biobanks and pharmaceutical and diagnostics companies that took place in Leipzig on the 21st of June 2018. It documents key points agreed on by all participating biobanks during the workshop thereby addressing several of the challenges identified. Although there are various possibilities for cooperation between academic biobanks and industry, this position article focuses exclusively on projects where academic biobanks give access to their biosamples and related data to industry partners. In doing so it considers the general conditions/framework and procedures in the German biobanking environment and raises ethical, legal, and procedural issues to be addressed when initiating such collaborations. It intends to furnish a basis for further activities to foster cooperation with industry and to push an overarching national coordination process. The final aim is to develop GBN-recommendations. Of course, many hospitals already have clear regulations on collaboration(s) with industry partners. These naturally take precedence for the GBA biobanks. However, where interest exists, GBN/GBA recommendations could help to induce changes to existing local policies nonetheless.

Objectives: The aim of this study was to provide an overview of the methodological characteristics and compare the assessment methods applied in health technology assessments (HTAs) of public health interventions (PHIs)., Methods: We defined a PHI as a population-based intervention on health promotion or for primary prevention of chronic or nonchronic diseases. HTAs on PHIs were identified by systematically searching the Web pages of members of international HTA networks. We included only full HTA reports published between 2012 and 2016. Two reviewers extracted data on the methods used to assess effectiveness/safety, as well as on economic, social, cultural, ethical, and legal aspects using a-priori standardized tables., Results: We included ten HTAs provided by four different organizations. Of these, all reports assessed the effectiveness of the interventions and conducted economic evaluations, seven investigated social/cultural aspects, and four each considered legal and ethical aspects, respectively. Some reports addressed applicability, context/setting, and intervention fidelity issues in different ways. We found that most HTAs adapted their methods to some extent, for example, by including nonrandomized studies, expanding the search strategy, involving stakeholders, or applying a framework to guide the HTA process., Conclusions: Our analysis provides a comprehensive overview of methods applied in HTAs on public health interventions. We found that a heterogeneous set of approaches is used to deal with the challenges of evaluating complex public health interventions.

Background: Conducting a health technology assessment (HTA) of public health interventions (PHIs) poses some challenges. PHIs are often complex interventions, which affect the number and degree of interactions of the aspects to be assessed. Randomized controlled trials on PHIs are rare as they are difficult to conduct because of ethical or feasibility issues. The aim of this study is to provide an overview of the methodological characteristics and to compare the applied assessment methods in HTAs on PHIs., Methods: We will systematically search HTA agencies for HTAs on PHIs published between 2012 and 2016. We will identify the HTAs by screening the webpages of members of international HTA organizations. One reviewer will screen the list of HTAs on the webpages of members of international HTA organization, and a second review will double-check the excluded records. For this methodological review, we define a PHI as a population-based intervention on health promotion or for primary prevention of chronic or non-chronic diseases. Only full HTA reports will be included. At maximum, we will include a sample of 100 HTAs. In the case that we identify more than 100 relevant HTAs, we will perform a random selection. We will extract data on effectiveness, safety and economic as well as on social, cultural, ethical and legal aspects in a priori piloted standardized tables. We will not assess the risk of bias as we focus on exploring methodological features. Data extraction will be performed by one reviewer and verified by a second. We will synthesize data using tables and in a structured narrative way., Discussion: Our analysis will provide a comprehensive and current overview of methods applied in HTAs on PHIs. We will discuss approaches that may be promising to overcome the challenges of evaluating PHIs.

Hospitals in Germany employ increasing numbers of foreign-born and foreign-trained (FB&FT) physicians. Studies have investigated how FB&FT physicians experience their professional integration into the German healthcare system, however, the perspectives of stakeholders working with and shaping the work experiences of FB&FT physicians in German hospitals have so far been neglected. This study explores relevant stakeholders' opinions and attitudes towards FB&FT physicians-which likely influence how these physicians settle in-and how these opinions were formed. We conducted a qualitative interview study with 25 stakeholders working in hospitals or in health policy development. The interviews were analyzed within a constructivist research paradigm using methods derived from Grounded Theory (situational analysis as well as open, axial and selective coding). We found that stakeholders tended to focus on problems in FB&FT physicians' work performance. Participants criticized FB&FT physicians' work for deviating from presumably shared professional standards (skill or knowledge and behavioral standards). The professional standards invoked to justify problem-focused statements comprised the definition of an ideal behavior, attitude or ability and a tolerance range that was adapted in a dynamic process. Behavior falling outside the tolerance range was criticized as unacceptable, requiring action to prevent similar deviations in the future. Furthermore, we derived three strategies (minimization, homogenization and quality management) proposed by participants to manage deviations from assumed professional standards by FB&FT physicians. We critically reflect on the social processes of evaluation and problematization and question the legitimacy of professional standards invoked. We also discuss discriminatory tendencies visible in evaluative statements of some participants as well as in some of the strategies proposed. We suggest it will be key to develop and implement better support strategies for FB&FT physicians while also addressing problematic attitudes within the receiving system to further professional integration.