bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a novel vector for siRNA delivery based on arginine‐modified polyvinylamine
Authors: Lin Mei , Lin Aizhu , Huang Sheng , Liu Tianhui , Ke Fang , Qiu Deshun , Lin Xuefeng , Luo Daoshu
Published: March 2022

An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: high gene transfection efficiency and low cytotoxicity. In this work, arginine was used to modify polyvinylamine (PVAm) to form a novel PVAm derivative (PVAm‐Arg) for siRNA delivery and the derivative was characterized using Fourier transform infrared spectroscopy. PVAm‐Arg/siRNA complexes were formed by the self‐assembly method. The zeta potential and size of the complexes were measured using electrophoretic light scattering and dynamic light scattering, respectively. The siRNA binding capacity of PVAm‐Arg was assessed using gel retardation assay. The results showed that PVAm‐Arg derivatives can bind siRNA effectively and form complexes with sizes of about 72 ± 2 nm. What is more, the ability of PVAm‐Arg to condense siRNA was better than that of PVAm. Cytotoxicity assay with RSC96 cells also showed that PVAm‐Arg had lower cytotoxicity compared with PVAm. In in vitro cellular uptake assay, PVAm‐Arg showed good transfection efficiency. Therefore, we concluded that PVAm‐Arg would be a promising candidate as a gene delivery vector. © 2022 Society of Industrial Chemistry.
Identification and Analysis of the Impurities for Triethylboron by GC‐MS Method
Authors: Su Pengfei , E Xiu‐tian‐feng , Wang Jingna , Zhu Yanlong , Zhang Gao , Chang Hai , Liu Ke , Meng Zihui
Published: March 2022

The detection and separation of impurities are crucial for the quality control of triethylboron. While the purity of triethylboron is the key factor for ballistic performance, impact accuracy, and storage safety. This work will explore a modified gas chromatography‐mass spectrometer method to detect and separate the impurities in synthesized triethylboron. They are identified as CH3CH2OCH2CH3, (CH3CH2)3B, (CH3CH2O)3B, CH3CH2CH2CH2B(CH3CH2)2 and (CH3CH2)3O3B3. Further, optimized GC conditions are demonstrated to quantify the synthesized triethylboron accurately and determine its purity. The purity of triethylboron is 96.39 % via a normalization method with high accuracy (RSD=0.05 %). The optimized GC conditions were as follows: a hydrogen flame ionization detector, nitrogen as carrier gas whose pathway was installed with a water trap and an oxygen trap, an HP‐5 capillary column (30 m×0.32 mm×0.25 μm) with the column temperature of 60 °C, an inlet temperature of 120 °C, the detector temperature of 150 °C, and an injection volume of 0.6 μL. This work demonstrates a simple and precise method to analyze the synthesized triethylboron and its impurities.
Effect of Block Structure of Copolyether Binder on Slow Cook‐Off Response of Composite Propellant
Authors: Wu Wei , Zhang Ximing , Ding Shanjun , Zhao Fengqi , Luo Yunjun
Published: March 2022

As the typical insensitive propellants, hydroxyl‐terminal block copolyether (HTPE) and hydroxyl‐terminal block copolyether (PET) propellant all belong to copolyether propellants. The two binders of propellants have different arrangements of copolyether structure. But, the effect of copolyether structure arrangement on the slow cook‐off behavior of propellants and its possible mechanism has been unknown. So, in this paper, the slow cook‐off behaviors of HTPE and PET propellants were tested. The result showed PET propellant responded more violently than HTPE propellant. Then, the changes of mass loss, explosion heat, and combustion performance of propellants during the cook‐off test were studied. Combined with the slow cook‐off behavior of AP and binders, the mechanism of block structure effect on slow cook‐off response of propellant was proposed. It expressed that, the binders of HTPE and PET propellant all degraded into liquid products due to the copolyether structure; but the block structure has a significant effect on the chain scission process of copolyether binder, which makes slight degradation and the mild response to slow cook‐off for HTPE propellant. While the binder of PET propellant with the random structure degraded seriously, making more mass loss, bigger explosion heat, and worse combustion performance, the PET propellant responds violently to slow cook‐off.
CRISPR/Cas9 unveils the dynamics of the endogenous µ‐opioid receptors on neuronal cells under continuous opioid stimulation
Authors: Shimizu Satoshi , Shiraki Atsuko
Published: March 2022

Long‐term opioid use develops tolerance and attenuates analgesic effects. Upon activation, µ‐opioid receptors (MOPs) are internalized and directed to either recycling or degradation pathway. Ligand stimulation also promotes de novo MOP synthesis. These processes collaboratively regulate MOP expression and play critical roles in tolerance development. However, there is limited understanding of how the endogenous MOP expression changes after prolonged opioid administration because previous analyses have focused on individual processes using overexpression systems, which ignored physiological regulation. Another fundamental problem is the unavailability of commercial antibodies to detect the low expression of endogenous MOP in neuronal systems. Here, we established a neuronal cell line to detect endogenous MOP with sufficient sensitivity using CRISPR/Cas9 technology. We incorporated the hemagglutinin sequence into the MOP gene of the SH‐SY5Y cell. The genome‐editing did not significantly impair MOP functions such as MOP internalization or the downstream signaling. The clone was differentiated into a state similar to the primary culture undergoing treatment with all‐trans retinoic acid, followed by brain‐derived neurotrophic factor. Upon continuous stimulation with MOP ligands, endogenous MOP constantly decreased up to 48 h. The expression level was maintained at a certain level following this period, depending on the ligand properties. DAMGO reduced MOP from the cell surface by about 70%, while morphine did so by 40%. Our results indicate that even a few days of opioid administration could significantly reduce the MOP expression level. Our cell line could be a potential tool to investigate the molecular mechanisms underlying the problems caused by long‐term opioid use.
Plasma Treatment of Ga‐Doped ZnO Nanorods
Authors: Micova Julia , Remes Zdenek , Artemenko Anna , Buryi Maksym , Lebeda Miroslav , Chang Yu Ying
Published: March 2022

A comparative study of structural, optical properties of plasma‐treated Ga‐doped ZnO nanorods (GZO NRs) prepared by hydrothermal growth is presented, which provides an economical technology for fast production. Annealing in air followed by plasma treatment has been found to be an effective way of purification of ZnO NRs. The plasma hydrogenation and oxidation are done at room temperature in an inductively coupled plasma (ICP) reactor. The properties of plasma‐treated GZO NRs are investigated using various characterization methods, such as scanning electron microscopy (SEM), Raman, Fourier transform infrared (FTIR), X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), and electron paramagnetic resonance (EPR) spectroscopy. The SEM confirms the hexagonal shape of all GZO NRs. XPS reveals the presence of metallic Ga as well as Ga2O3 on GZO NRs surface. XRD has detected hexagonal (P63mc) ZnO phase in all samples with additional diffraction pattern in powder that has not been plasma treated. Plasma treatment does not affect the position of FTIR signals but changes the intensity of some absorption peaks. EPR shows a dominant signal with a g‐factor of 1.96. Plasma treatment of GZO samples affects its intensity.
A simple and rapid chromatographic method for determination of naproxen and nabumetone in tablets
Authors: Puttanapitak Piriyaporn , Chokesinlapasart Suchanun , Suntornsuk Leena , Phechkrajang Chutima , Prutthiwanasan Brompoj
Published: March 2022

A simple, rapid, and cost‐effective chromatographic method for determination of naproxen and nabumetone using a guard column was developed. Factors affecting separation (i.e., types of stationary phase and types and compositions of mobile phase) were optimized. Naproxen and nabumetone were completely resolved (Rs > 2.0) on a C18 guard column (10 × 4.0 mm, 5 μm) in 5 min using a mobile phase consisting of 2% v/v acetic acid (in water) and acetonitrile (75:25 v/v). Method validation was performed in terms of specificity, range, linearity, precision, and accuracy. The method showed a linear relationship (r2 > 0.999) in a range of 2–30 μg/mL, good precision (%RSD < 0.97), accuracy (%recovery of 98.8–100.5%), and specificity (peak purity indices >99%) for the determination of naproxen and nabumetone. The method was applied for quantitation of naproxen and nabumetone in tablets. Results were complied with the United State Pharmacopeia 2021 limits (90.0–110.0 and 95.0–105.0% for naproxen and nabumetone, respectively). The use of the guard column proved to be efficient, fast, and economical due to less solvent consumption and waste production. In addition, this approach benefits the quality control of pharmaceuticals in less industrial countries with limited resources.
Angle of progression measured using transperineal ultrasound for prediction of uncomplicated operative vaginal delivery: systematic review and meta‐analysis
Authors: Nassr A. A. , Hessami K. , Berghella V. , Bibbo C. , Shamshirsaz A. A. , Shirdel Abdolmaleki A. , Marsoosi V. , Clark S. L. , Belfort M. A. , Shamshirsaz A. A.
Published: March 2022

Objective

To determine whether intrapartum transperineal ultrasound measurement of the angle of progression (AoP) during the second stage of labor can predict uncomplicated operative vaginal delivery (OVD) using vacuum or forceps extraction.

Methods

A systematic search in PubMed, EMBASE, Scopus, Web of Science and Google Scholar was performed from inception to February 2021. Studies assessing the predictive accuracy of AoP, measured using intrapartum transperineal ultrasound, for uncomplicated OVD, defined as successful vaginal delivery within three pulls using forceps or no more than two detachments of the vacuum extractor cup, were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. Summary receiver‐operating‐characteristics (ROC) curves, pooled sensitivity and specificity, area under the ROC curve (AUC) and summary likelihood ratios (LRs) were calculated.

Results

Seven studies reporting on a total of 782 patients undergoing OVD were included in this systematic review and meta‐analysis. Second‐stage AoP measured during maternal rest had a pooled sensitivity of 80% (95% CI, 59–92%) and specificity of 89% (95% CI, 76–95%), with a LR+ of 7.3 (95% CI, 3.1–15.8) for uncomplicated OVD. AoP measured during active pushing had a sensitivity of 91% (95% CI, 85–94%) and specificity of 83% (95% CI, 69–92%), with a LR+ of 5.4 (95% CI, 2.7–10.6) for uncomplicated OVD. The performance of AoP measured at rest was particularly high in nulliparous women, with a sensitivity of 87% (95% CI, 75–94%) and specificity of 90% (95% CI, 82–94%) for uncomplicated OVD.

Conclusion

AoP may be a reliable predictor for uncomplicated OVD when measured during the second stage of labor, especially in nulliparous women. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Pay-To-Pass: Evolving Online Systems That Undermine the Integrity of Student Work
Authors: Chibry Nancy , Kurz Ebba U.
Published: March 2022

In an age where information is available at our fingertips, students in the post-secondary environment have equally ready access to resources that can be supportive of their academic development or academically questionable. In this chapter, we describe the pervasiveness of pay-to-pass websites in the Canadian post-secondary context. We distinguish pay-to-pass websites from other forms of contract cheating by defining them as sites encouraging students to share and access course material, assessments, and notes for academic and personal gain, as well as those providing real-time academic support. This chapter is a reflection on the nature and impact of these sites and explores a three-pronged approach to addressing the challenges posed by them on the upholding of academic integrity in post-secondary education.
Academic Integrity in Work-Integrated Learning (WIL) Settings
Authors: Miron Jennifer B.
Published: March 2022

This chapter highlights the imperative for attention to, and action in, the promotion of academic integrity in work-integrated learning (WIL) settings across post-secondary programs. The importance of such efforts are closely tied to the efforts of strengthening ethical comportment with graduates who will go on to contribute to client care, client service, leadership, and research that will directly impact members of the public, hiring organizations, and global systems. WIL settings provide invaluable opportunities for students to learn essential skills and acculturate to professional ethical values through real world experiences. The experiential learning that happens in these settings helps influence the professionalization of students, encouraging safe, ethical practice that benefits those receiving care/service, future employers, and society. Since WIL is offered in both college and university settings and occurs across a number of professional and service programs, it has the potential to significantly influence a vast and varied number of professionals entering numerous career paths around the world. All members of learning communities in post-secondary organizations have a responsibility to understand their roles and opportunities in supporting, maintaining, and promoting academic integrity across WIL settings. While the narrative for the chapter is Canadian, the observations and recommendations may be relevant in other countries, where WIL plays a significant role in the education and development of professionals and service providers across a number of professions and trades.
Teaching the Teachers: To What Extent Do Pre-service Teachers Cheat on Exams and Plagiarise in Their Written Work?
Authors: Peters Martine , Fontaine Sylvie , Frenette Eric
Published: March 2022

Very little is known about preservice teachers’ actions when it comes to plagiarizing and cheating in their university work. This is particularly the case in Quebec, Canada. It is important to know to what extent these students commit academic misconduct as they will ultimately become the role models who will shape future generations of learners. This chapter reports on a study of this important issue. An online questionnaire was used to survey preservice teachers (n = 573) in five Quebec universities in winter 2018. The majority of participants were between the ages of 18 to 25 and were studying to be kindergarten, primary, special education or high school teachers. The questionnaire contained items about demographic information as well as items on methods of cheating, peers’ influence, perception of control, goal of performance and engaging in studying. Preservice teachers also answered questions that were used to control for social desirability bias. Results showed that some of them reported participating in academic misconduct. Fewer participants reported cheating on exams while studying at university (15.2%) than when they were in high school (34.9%). They believe that the best ways to plagiarise on written assignment are reusing one’s previous work (47.6%), asking somebody else to do the assignment (38.6%), and collaborating with peers (37.2%) while the best ways to cheat on exams would be using hidden material (63%), looking at the neighbour’s copy (55.7%) and using electronic devices (31.9%). Four interpretations for the preservice teacher actions are given: they commit academic misconduct because they want to succeed, because they have poor studying habits which lead them to make poor decisions, because of the cheating culture in which they evolve, and because of the cheating patterns they develop. Recommendations for teacher education programs conclude the article.
Academic Integrity Across Time and Place: Higher Education’s Questionable Moral Calling
Authors: Christensen Hughes Julia
Published: March 2022

In this chapter, I call on Canada’s higher education institutions to embrace Veritas (truth), in every aspect of the academy. Academic integrity must transcend discussions of student misconduct and apply to all that we are—our history, our research, our curriculum, our pedagogy, our purpose. Tracing Western higher education’s development from medieval times in Europe, through to the US and Canada, I make the case that the academy has paradoxically been both a dominating and liberating force since its inception. While imposing Western conceptions of morality and truth that have shifted over time, and supporting the imperialist ambitions of Church, monarchy and state, higher education has also elevated its graduates to positions of influence within society and advanced national aims. Despite credos of truth telling and missions of character development, higher education’s moral calling has been—and remains—highly questionable. Given the complex challenges the world is facing today, and the need for Canadian institutions of higher learning to confront their colonial roots, it is time for us to critically examine this history and explicitly (re)position integrity at the core of Canada’s higher education institutions.
Changing “Hearts” and Minds: Pedagogical and Institutional Practices to Foster Academic Integrity
Authors: McNeill Laurie
Published: March 2022

This chapter shares findings of and recommendations from a three-year initiative at the University of British Columbia to develop and assess enhanced and explicit instruction in academic integrity in first-year writing courses, an enterprise that now involves 42 faculty members teaching up to 5000 students each year. This project began from the appreciation that, as an institution, we needed to close the gap between our expectations of academic integrity and students’ understanding of those expectations, and to make explicit what is often treated as assumed understanding. This approach was intended to help students develop more robust knowledge and appreciation for academic integrity as a core element of the academic community to which they now belong. Drawing on the qualitative and quantitative data we gathered from students and faculty, including surveys, focus groups, misconduct reports, and interviews, I illustrate how what I call “pedagogies of integrity” have led to improved uptake by students (and instructors) of academic integrity as both theory and practice, resulting in a change in the number as well as type of academic misconduct cases, and have led to significant insights about the place of academic integrity in larger conversations about student belonging, wellness, and access. I share not only how the instructors in this project changed the conversation in their own courses, but also how these discussions are resonating across disciplines and faculties of our campus and beyond. Finally, I outline recommendations for next steps in policy and practice that these findings suggest.
Using Quality Assurance Frameworks to Support an Institutional Culture of Academic Integrity at Canadian Universities
Authors: Thacker Emma J. , McKenzie Amanda
Published: March 2022

In Canada, there is a national academic quality assurance framework—the Canadian Degree Qualifications Framework (CDQF) that guides quality assurance standards within universities across the provinces and territories. These standards exist to support the quality and consistency of postsecondary academic programming in Canada, and provide mechanisms for quality enhancement. The CDQF is supported by further quality assurance mechanisms at the provincial level. While the CDQF includes the notion of academic integrity as a learning outcome requirement, the implementation and review of this quality indicator across the sector is nebulous. The ongoing support for a culture of academic integrity requires a holistic approach, which includes the alignment of various policies and processes. It also involves the inclusion of academic integrity best practices into quality assurance processes, such as curriculum development and program review. In this chapter we discuss several quality assurance tools used in Canadian universities, with a focus on Ontario institutions, and discuss opportunities to leverage them to support academic integrity. The CDQF and provincial/territorial quality assurance frameworks should be better utilized for a holistic response to academic misconduct, to strengthen teaching and learning, and develop a culture of integrity in higher education. Opportunities within cyclical program review, curriculum mapping and educational development are discussed to highlight opportunities for academic integrity specialists, quality assurance staff, faculty, and policy makers to raise academic integrity awareness and weave best practices across an institution. Implications for the community college sector are also included. Recommendations can be applied to postsecondary institutions across Canada and integrated with quality assurance practices promoted by the Quality Assurance Agency (QAA) and others academic integrity advocates around the world.
Student Integrity Violations in the Academy: More Than a Decade of Growing Complexity and Concern
Authors: Christensen Hughes Julia , Eaton Sarah Elaine
Published: March 2022

Academic misconduct in Canada is a growing and complex concern, worthy of increased attention and concerted action. Yet, the press appears to be more actively engaged (at least more vocal) in raising concerns about integrity violations than many in our post-secondary institutions. This chapter presents a synopsis of the seminal work by Christensen Hughes and McCabe (in the Canadian Journal of Higher Education 36: 1–21, 2006), followed by an exploration of its treatment by the press—in particularMacLean’smagazine—following its release. We also present select stories of student misconduct as reported by the Canadian press from 2010 to 2020. From a review of these contributions, we suggest that misconduct in the academy appears to be growing in complexity, severity and by the variety of third-party stakeholders involved. Types of cheating identified in this review include: the use of wearable, wireless high-tech devices for communicating with accomplices; paying (bribing) TAs for answers and inflated grades; exam impersonation; plagiarism; and contract cheating (customized essay buying from freelance writers and essay sweatshops). Explanations provided in the press for these behaviours, include increasing numbers of international students, the proliferation of contract cheating services, and increased use of on-line assessment, resulting from the Covid-19 pandemic. The chapter concludes with a call to action, for all post-secondary institutions, to a greater commitment to academic integrity, including stepping up efforts to educate faculty and students as well as to embrace innovation in assessment design and invigilation practice. We also suggest advocacy for introducing laws that will help to deter contract cheating services.
Accountability, Relationality and Indigenous Epistemology: Advancing an Indigenous Perspective on Academic Integrity
Authors: Lindstrom Gabrielle E.
Published: March 2022

Although the notion of academic integrity is advanced as a Western construct, Indigenous ways of conceptualising and mobilizing this construct represent a vast, diverse and enduring knowledge system that encompasses not only how sources of knowledge are attributed, but also serves as one of the ontological pillars that upholds honesty and truth-telling within a relationally oriented epistemology. Written from an Indigenous perspective, this chapter invites readers to critically reflect on the ways that academic integrity, as an ethical pillar of the Western academy, relies on institutionalized protocols that privilege a specific methodology of citation and referencing that elevates the written word whilst excluding Indigenous methodologies that are embedded within an ethic of truth-telling and relational accountability. Grounded in the scholarship that surrounds Indigenous knowledge as a participatory way of knowing and utilizing a values-based analysis, I highlight the conceptual parallels between Western understandings of academic integrity and an Indigenous relational epistemology that is rooted in accountability. In today’s social climate of reconciliation, academic institutions across Canada are seeking avenues to decolonize their pedagogies and practices. One such avenue is in the area of academic integrity which is underlain with distinct and established ways of transmitting knowledge that have all too often left Indigenous knowledge systems to exist as alternative, or less rigorous, approaches to knowledge production. Movement towards a more equitable, critical and comprehensive understanding of how we, as scholars, are being accountable to those voices that inform and shape our own requires the consideration of a trans-systemic approach.
Complexity, Crises and Coping Strategies
Authors: Head Brian W.
Published: March 2022

Wicked problems are shaped through complex system dynamics and involve multiple stakeholders. Public concern about wicked problems is often generated through crises that provoke awareness and intensify a wide sense of urgency. This chapter outlines some key aspects of crises that affect how wicked problems are perceived, debated and managed. Importantly, some ‘creeping’ crises develop gradually over an extended period with slow cumulative impacts, and there is uncertainty about when to accord them high priority. Other crises are immediate and fast-moving, giving rise to general acceptance of the need for rapid responses. In many cases, there will be serious disagreements about policy responses, owing to the complexity of causal factors and the diversity of stakeholder values and opinions. Some crisis-induced challenges can be well managed in the short term, leading to a return towards ‘normal’ life, but most responses do not explicitly tackle the complex underlying causes that generate the crises. Finally, it is suggested that the governance of wicked problems is less about designing elegant science-based solutions and more about implementing ‘coping’ strategies, which manage uncertainties, strengthen community capabilities and build resilience across all sectors—social, economic and environmental.
Managing Environmental and Sustainability Challenges
Authors: Head Brian W.
Published: March 2022

Wicked problems and robust debates abound in environmental policy at local, national and global levels. Over several decades, governments have responded with policies to mitigate industrial pollution, slow the rapid depletion of scarce natural resources and protect biodiversity and ecological systems. The precautionary principle has been invoked to seek thorough assessment of environmental risks before approving economic development projects and technological innovations that might damage ecological assets and human health. Scientific researchers and community groups have lobbied for strong measures to protect biodiversity and promote resilient eco-systems. Resistance to reform has generally been led by conservative parties, corporate media networks and large business firms in traditional industry sectors. Policies for environmental protection have been developed by most national governments, in conjunction with international agreements that encourage collective action. The toolkit of policy instruments has expanded, including regulatory standards and market-based incentives. The role of scientific expertise in providing policy advice on environmental issues has been vital, but controversial. The chapter explores how science interacts with other sources of knowledge and opinion among practitioners and stakeholders. Climate change policy is analysed as an example of interconnected wicked problems, along with brief references to other environmental issues.
Improving Social Well-Being and Social Equity
Authors: Head Brian W.
Published: March 2022

Protecting and enhancing the well-being of citizens is a central goal of modern governments. The specific social programs adopted in various countries reflect their local political and economic contexts. The range of problems considered is very extensive—such as public health services, education and training, social support services, crime and corrections and issues concerned with discrimination in relation to age, gender, ethnicity and religion. The core pillars of social policy—especially income support, health, education, social services and civil rights—broadly constitute the modern ‘welfare state’. All the social reforms were controversial when first proposed in earlier times. As public expectations gradually increased, so political ambitions correspondingly shifted. In most democracies, the problem of deep and enduring poverty, along with gender-based discrimination, came to be seen as unacceptable features of advanced societies. But many programs have remained controversial. Thus, the key dimensions of wicked problems—complexity, disagreement and uncertainty—have permeated social policy debates. The chapter includes a brief discussion of two case studies of wicked problems in action—policies to tackle homelessness and policies regulating drug use.
Policy Innovation in Turbulent Times
Authors: Head Brian W.
Published: March 2022

Innovative solutions are increasingly recommended because many of the old-style solutions (see Chapter 10.1007/978-3-030-94580-0_3) are found to be ineffective. This chapter explores the felt need for greater innovation in tackling social, economic, technological and bio-health issues. Improved knowledge and understanding are required not only to appreciate and foster innovations, but also to identify appropriate ways to regulate new technologies. The chapter considers recent work on design methods for facilitating social innovation. Much of this work is aimed at the local level and place-based contexts, rather than aspiring to design mainstream programs at a national level. The chapter considers the arguments in favour of social experimentation and co-design processes for addressing wicked problems. It concludes with some observations on the contemporary politics of populism and opinion-based policy ideas.
Die somatische Dysfunktion der Halswirbelsäule und ihr komplexes klinisches Bild
Authors: Wagner Florian Max-Josef
Published: March 2022

Die segmentale und somatische Dysfunktion der Halswirbelsäule kann aufgrund komplexer funktionell-anatomischer und neurophysiologischer Verschaltungen dem Untersucher einen variantenreichen, aber teils schwer nachvollziehbaren Symptomkomplex bieten. Auf Grundlage von zervikotrigeminalen und intersegmentalen Konvergenzen im Bereich des Rückenmarks der Halswirbelsäule und des Hirnstammes lassen sich diese Symptome, die als zervikozephales Syndrom und Zervikobrachialgie zusammengefasst werden, nachvollziehen. Eine fundierte manualmedizinische Untersuchung kann, nach Ausschluss bedrohlicher Differenzialdiagnosen, das Vorliegen einer Blockierung der Halswirbelsäule als mögliche Ursache oder als Teilaspekt der Beschwerden demaskieren. Eine manualmedizinische Behandlung mit dem Setzen gezielter antinozizeptiver propriozeptiver Reize ist dann eine sinnvolle therapeutische Option.
Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans
Authors: Elbe Annika , Foerster Kathrin Isabelle , Blank Antje , Rose Peter , Burhenne Jürgen , Haefeli Walter Emil , Mikus Gerd
Published: March 2022

Purpose

To investigate the suitability of microdosed oral omeprazole for predicting CYP2C19 activity in vivo in combination with simultaneous assessment of CYP3A and CYP2D6 activity using both microdosed midazolam and yohimbine.

Methods

An open, fixed-sequence study was carried out in 20 healthy participants. Single microdosed (100 µg) and therapeutic (20 mg) doses of omeprazole were evaluated without comedication and after administration of established CYP2C19 perpetrators fluconazole (inhibition) and rifampicin (induction). To prevent degradation of the uncoated omeprazole microdose, sodium bicarbonate buffer was administered. The pharmacokinetics of omeprazole and its 5-hydroxy-metabolite were assessed as well as the pharmacokinetics of midazolam and yohimbine to estimate CYP3A4 and CYP2D6 activity.

Results

Calculated pharmacokinetic parameters after administration of 100 µg and 20 mg omeprazole in healthy subjects suggest dose proportionality. Omeprazole clearance was significantly decreased by fluconazole from 388 [95% CI: 266–565] to 47.2 [42.8–52.0] mL/min after 20 mg omeprazole and even further after 100 µg omeprazole (29.4 [24.5–35.1] mL/min). Rifampicin increased CYP2C19-mediated omeprazole metabolism. The omeprazole hydroxylation index was significantly related to omeprazole clearance for both doses. Both fluconazole and rifampicin altered CYP3A4 activity whereas no change of CYP2D6 activity was observed at all.

Conclusions

Microdosed oral omeprazole is suitable to determine CYP2C19 activity, also during enzyme inhibition and induction. However, the administration of sodium bicarbonate buffer also had a small influence on all victim drugs used.

Trial registration

EudraCT: 2017–004270-34.
BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma: a real-life experience
Authors: Stefoni Vittorio , Argnani Lisa , Carella Matteo , Casadei Beatrice , Morigi Alice , Lolli Ginevra , Broccoli Alessandro , Pellegrini Cinzia , Nanni Laura , Coppola Paolo Elia , Zinzani Pier Luigi
Published: March 2022

Purpose

One of the most critical issues in the management of Hodgkin lymphoma (HL) patients who resulted as primary relapsed or refractory is to obtain a minimal disease status before autologous stem cell transplantation (ASCT). Finding a salvage regimen able to induce this status without severe toxicity would represent a major achievement in this setting.

Methods

A single‐center retrospective study was conducted to assess effectiveness and safety of BEGEV (bendamustine, gemcitabine, and vinorelbine) regimen as first salvage setting prior to ASCT in HL patients.

Results

Forty-three patients were treated in our institution between October 2017 and November 2020. Median age at BEGEV therapy was 35.0 years (range 17.2– 70.0), and the median time from frontline therapy to the first cycle of BEGEV was 79.5 days (range 4–2267). At the end of treatment, 31 patients achieved a complete response (CR), with an overall response rate of 76.7%. Forty-one patients harvested CD34+ cells and 35/43 (81.4%) patients underwent ASCT. With a median follow‐up of 22 months, 4 CR patients had disease relapse, yielding an estimated disease-free survival of 73.9% at 34 months. The estimated 2‐year progression-free survival was 66.7%. Response to first-line chemotherapy did not significantly influence prognosis.

Conclusions

BEGEV regimen was well tolerated, and reversible haematological toxic effects were the most common adverse events. Real-life data on BEGEV regimen as first salvage setting showed a relevant rate of objective responses and a limited myelotoxicity with no impairment of a subsequent mobilization of peripheral blood stem cells.
Cancer-related fatigue in patients treated with mistletoe extracts: a systematic review and meta-analysis
Authors: Pelzer Florian , Loef Martin , Martin David D. , Baumgartner Stephan
Published: March 2022

Purpose

Cancer-related fatigue remains one of the most prevalent and distressing symptoms experienced by cancer patients. Effective treatments for cancer-related fatigue are needed. The objective of this meta-analysis is to determine the impact of mistletoe extracts as a pharmacological treatment for the management of cancer-related fatigue.

Methods

We included randomized clinical trials (RCTs) and non-randomized studies of interventions (NRSIs) in cancer patients. Inclusion criteria were cancer-related fatigue severity or prevalence as an outcome and testing of mistletoe extracts compared to control groups. We searched Medline (EuropePMC), Embase, the Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and opengrey.org through October 2020. We assessed the risk of bias using the Cochrane risk of bias tools for RCTs and NRSIs and conducted a meta-analysis.

Results

We performed one meta-analysis with 12 RCTs, including 1494 participants, and one meta-analysis with seven retrospective NRSIs, including 2668 participants. Heterogeneity between the studies was high in both meta-analyses. Most studies had a high risk of bias. A random-effects model showed for RCTs a standardized mean difference of –0.48 (95% confidence interval –0.82 to –0.14; p = 0.006) and for NRSIs an odds ratio of 0.36 (95% confidence interval 0.20 to 0.66; p = 0.0008).

Conclusion

Treatment with mistletoe extracts shows a moderate effect on cancer-related fatigue of similar size to physical activity. These results need to be confirmed by more placebo-controlled trials. Future trials should investigate different treatment durations and their effect on cancer-related fatigue in post-treatment cancer survivors.

Trial registration.

This meta-analysis has been registered under the PROSPERO registration number CRD42020191967 on October 7, 2020.
Specific and sensitive GC–MS analysis of hypusine, Nε-(4-amino-2-hydroxybutyl)lysine, a biomarker of hypusinated eukaryotic initiation factor eIF5A, and its application to the bi-ethnic ASOS study
Authors: Baskal Svetlana , Kaiser Annette , Mels Catharina , Kruger Ruan , Tsikas Dimitrios
Published: March 2022

Hypusination is a unique two-step enzymatic post-translational modification of the Nε-amino group of lysine-50 of the eukaryotic initiation factor 5A (eIF5A). We developed a specific and sensitive gas chromatography–mass spectrometry (GC–MS) method for the measurement of biological hypusine (Hyp), i.e., Nε-(4-amino-2-hydroxybutyl)lysine. The method includes a two-step derivatization of Hyp: first esterification with 2 M HCl in CH3OH (60 min, 80 °C) to the methyl ester (Me) and then acylation with penta-fluoro-propionic (PFP) anhydride in ethyl acetate (30 min, 65 °C). Esterification with 2 M HCl in CD3OD was used to prepare the internal standard. The major derivatization product was identified as the un-labelled (d0Me) and the deuterium-labelled methyl esters (d3Me) derivatives: d0Me-Hyp-(PFP)5 and d3Me-Hyp-(PFP)5, respectively. Negative-ion chemical ionization generated the most intense ions with m/z 811 for d0Me-Hyp-(PFP)5 and m/z 814 for the internal standard d3Me-Hyp-(PFP)5. Selected-ion monitoring of m/z 811 and m/z 814 was used in quantitative analyses. Free Hyp was found in spot urine samples (10 µL) of two healthy subjects at 0.60 µM (0.29 µmol Hyp/mmol creatinine) in the female and 1.80 µM (0.19 µmol Hyp/mmol creatinine) in the male subject. The mean accuracy of the method in these urine samples spiked with 1–5 µM Hyp was 91–94%. The limit of detection (LOD) of the method is 1.4 fmol Hyp. The method was applied to measure the urinary excretion rates of Hyp in healthy black (n = 38, age 7.8 ± 0.7 years) and white (n = 41, age 7.7 ± 1.0 years) boys of the Arterial Stiffness in Offspring Study (ASOS). The Hyp concentrations were 3.55 [2.68–5.31] µM (range 0.54–9.84 µM) in the black boys and 3.87 [2.95–5.06] µM (range 1.0–11.7 µM) in the white boys (P = 0.64). The creatinine-corrected excretion rates were 0.25 [0.20–0.29] µmol/mmol (range 0.11–0.36 µmol/mmol) in the black boys and 0.26 [0.21–0.30] µmol/mmol (range 0.10–0.45 µmol/mmol) in the white boys (P = 0.82). These results suggest that there is no ethnic-related difference in the ASOS population in the eIF5A modification. Remarkable differences were found between black and white boys with respect to correlations of urinary Hyp with amino acids and advanced glycation end-products of Lys, Arg and Cys. Deoxyhypusine, formally the direct precursor of Hyp, seems not to be excreted in the urine by healthy subjects.
Understanding the challenges faced by Michigan’s family farmers: race/ethnicity and the impacts of a pandemic
Authors: Taylor Dorceta E. , Farias Lina M. , Kahan Lia M. , Talamo Julia , Surdoval Alison , McCoy Ember D. , Daupan Socorro M.
Published: March 2022

Michigan is a critical agricultural state, and small family farms are a crucial component of the state’s food sector. This paper examines how the race/ethnicity of the family farm owners/operators is related to farm characteristics, financing, and impacts of the pandemic. It compares 75 farms owned/operated solely by Whites and 15 with People of Color owners/operators. The essay examines how farmers finance their farm operations and the challenges they face doing so. The article also explores how the Coronavirus-19 (COVID-19) pandemic affected farming operations, the financial viability of farms, and how farmers responded to the challenges posed by the pandemic. The study found that People of Color farm owners/operators were younger than White farm owners/operators. The People of Color farm owners/operators tended to manage smaller farms for shorter periods than White farm owners/operators. Though two-thirds of the Farmers of Color owned their farms, they were more financially vulnerable than White farm owners/operators. The farmers studied had difficulty obtaining loans to finance their farms. Farmers reported increasing requests from people for food assistance during the pandemic. Farmers responded to the pandemic by participating in government programs such as the Farm to Families Food Box Program that purchased their produce. It allowed farmers to supply emergency food assistance programs with products from their farms. The products went to families receiving food assistance from soup kitchens, food banks, and other community-based nonprofits.
UAV swarm path planning with reinforcement learning for field prospecting
Authors: Puente-Castro Alejandro , Rivero Daniel , Pazos Alejandro , Fernandez-Blanco Enrique
Published: March 2022

There has been steady growth in the adoption of Unmanned Aerial Vehicle (UAV) swarms by operators due to their time and cost benefits. However, this kind of system faces an important problem, which is the calculation of many optimal paths for each UAV. Solving this problem would allow control of many UAVs without human intervention while saving battery between recharges and performing several tasks simultaneously. The main aim is to develop a Reinforcement Learning based system capable of calculating the optimal flight path for a UAV swarm. This method stands out for its ability to learn through trial and error, allowing the model to adjust itself. The aim of these paths is to achieve full coverage of an overflight area for tasks such as field prospection, regardless of map size and the number of UAVs in the swarm. It is not necessary to establish targets or to have any previous knowledge other than the given map. Experiments have been conducted to determine whether it is optimal to establish a single control for all UAVs in the swarm or a control for each UAV. The results show that it is better to use one control for all UAVs because of the shorter flight time. In addition, the flight time is greatly affected by the size of the map. The results give starting points for future research, such as finding the optimal map size for each situation.
Isotropic 3D compressed sensing (CS) based sequence is comparable to 2D-LGE in left ventricular scar quantification in different disease entities
Authors: Fenski Maximilian , Grandy Thomas Hiroshi , Viezzer Darian , Kertusha Stela , Schmidt Michaela , Forman Christoph , Schulz-Menger Jeanette
Published: March 2022

The goal of this study was to evaluate a three-dimensional compressed sensing (3D-CS) LGE prototype sequence for the detection and quantification of myocardial fibrosis in patients with chronic myocardial infarction (CMI) and myocarditis (MYC) compared with a 2D-LGE standard. Patients with left-ventricular LGE due to CMI (n = 33) or MYC (n = 20) were prospectively recruited. 2D-LGE and 3D-CS images were acquired in random order at 1.5 Tesla. 3D-CS short axis (SAX) images were reconstructed corresponding to 2D SAX images. LGE was quantitatively assessed on patient and segment level using semi-automated threshold methods. Image quality (4-point scoring system), Contrast-ratio (CR) and acquisition times were compared. There was no significant difference between 2D and 3D sequences regarding global LGE (%) (CMI [2D-LGE: 11.4 ± 7.5; 3D-LGE: 11.5 ± 8.5; p = 0.99]; MYC [2D-LGE: 27.0 ± 15.7; 3D-LGE: 26.2 ± 13.1; p = 0.70]) and segmental LGE-extent (p = 0.63). 3D-CS identified papillary infarction in 5 cases which was not present in 2D images. 2D-LGE acquisition time was shorter (2D: median: 06:59 min [IQR: 05:51–08:18]; 3D: 14:48 min [12:45–16:57]). 3D-CS obtained better quality scores (2D: 2.06 ± 0.56 vs. 3D: 2.29 ± 0.61). CR did not differ (p = 0.63) between basal and apical regions in 3D-CS images but decreased significantly in 2D apical images (CR basal: 2D: 0.77 ± 0.11, 3D: 0.59 ± 0.10; CR apical: 2D: 0.64 ± 0.17, 3D: 0.53 ± 0.11). 3D-LGE shows high congruency with standard LGE and allows better identification of small lesions. However, the current 3D-CS LGE sequence did not provide PSIR reconstruction and acquisition time was longer.
A Half Century of Progress in US Student Achievement: Agency and Flynn Effects, Ethnic and SES Differences
Authors: Shakeel M. Danish , Peterson Paul E.
Published: March 2022

Policymakers, conceptualized here as principals, disagree as to whether US student performance has changed over the past half century. To inform conversations, agents administered seven million psychometrically linked tests in math (m) and reading (rd) in 160 survey waves to national probability samples of cohorts born between 1954 and 2007. Estimated change in standard deviations (sd) per decade varies by agent (m: –0.10sd to 0.27sd, rd: –0.02sd to 0.12sd). Consistent with Flynn effects, median trends show larger gains in m (0.19sd) than in rd (0.04sd), though rates of progress for cohorts born since 1990 have increased in rd but slowed in m. Greater progress is shown by students tested at younger ages (m: 0.31sd, rd: 0.08sd) than when tested in middle years of schooling (m: 0.17sd, rd: 0.03sd) or toward the end of schooling (m: 0.06sd, rd: 0.02sd). Young white students progress more slowly (m: 0.28sd, rd: 0.09sd) than Asian (m: 46sd, rd: 0.28sd), black (m: 0.36sd, rd: 0.19sd), and Hispanic (m: 0.29sd, rd: 0.13sd) students. These ethnic differences generally attenuate as students age. Young students in the bottom quartile of the SES distribution show greater progress than those in the top quartile (difference in m: 0.08sd, in rd: 0.15sd), but the reverse is true for older students. Moderators likely include not only changes in families and schools but also improvements in nutrition, health care, and protection from contagious diseases and environmental risks. International data suggest that subject and age differentials may be due to moderators more general than just the United States.