bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Determination Theory and Technology Design
Authors: Peters Dorian , Calvo Rafael A.
Published: February 2023

This chapter reviews the breadth of work applying self-determination theory (SDT) to digital technology with a focus on how it informs design. SDT is especially well-suited and actionable within the technology design context. The chapter reviews advancements within specific domains, highlighting fields that have been productive with respect to SDT in technology, including games, health, and education. It then shifts to work that applies SDT to user experience and technology design across domains, including the METUX model, and it describes efforts to provide practitioners with SDT-based tools that bridge academic theory to design practice. The chapter concludes by identifying gaps and opportunities for future work. The aim is to pull together the disparate work across domains that has constituted SDT for technology research and provide a coherent foundation for building on this work synergistically into the future.
The Social Conditions for Human Flourishing
Authors: Ryan Richard M. , DeHaan Cody R.
Published: February 2023

In this chapter we review recent conceptualizations and research regarding the impact of political and economic systems on people’s thriving through their effects on basic needs for autonomy, competence, and relatedness. Self-determination theory (SDT) particularly stresses how thriving requires both access to resources (e.g., education, healthcare) and freedoms (e.g., rights for identity choice, freedom from discrimination). Illustrating this are studies using economic and philosophical models of capabilities and social primary goods, the positive effects of which are largely mediated by SDT’s basic needs. The chapter also includes discussion of how governments create compliance by either controlling or autonomy-supportive means, with differing effects. SDT supplies a critical and comparative perspective on both economic and political policies and practices using its criteria of meeting human needs.
Education as Flourishing
Authors: Ryan Richard M. , Reeve Johnmarshall , Kaplan Haya , Matos Lennia , Cheon Sung Hyeon
Published: February 2023

In the perspective of self-determination theory the central aim of education should be that of enhancing students’ flourishing. Flourishing involves not only the development of cognitive capacities but also capacities for agency, prosocial relationships, and psychological wellness. Strong evidence within self-determination theory, reviewed herein, shows how teaching styles that support students’ basic needs for autonomy, relatedness, and competence foster these aspects of flourishing, enhancing the quality of students’ engagement, learning, and social relationships. Also highlighted are how students’ motivation and agency reciprocally influence teachers’ tendency to be need supportive, such that interventions on both sides of the teacher-student relationship can enhance learning climates. Nonetheless, this body of evidence concerns optimizing need supports within existing school environments, which too often remain mired in policies, practices, and omnipresent evaluations that are not designed for student flourishing, and which instead often harm both students’ and teachers’ well-being and motivation. The chapter’s conclusion includes a call to broaden the criteria by which schools are evaluated to include process as well as outcome targets. Creating the best schools we can imagine entails the assessment and cultivation of what really matters (i.e., process targets) to student flourishing in both their present and future lives.
The Historical Political Economy of Colonialism
Authors: Guardado Jenny
Published: February 2023

This chapter surveys the literature on whether and which are the long-run economic legacies of European colonization today. From these works stands out the diversity of development experiences across and even within formerly colonized countries depending on the conditions encountered by colonizers, the latter’s identity, or the length of colonization, to name a few. However, most of these studies are based on comparisons among different types of colonization experiences and not vis-à-vis a scenario of no colonization, constituting a potential avenue for future research. Nonetheless, available findings allow researchers to identify and rank the effect of different colonial policies on key drivers of economic disparities today.
The Present and Future of Verbal Lie Detection
Authors: Vrij Aldert , Granhag Pӓr Anders , Leal Sharon , Fisher Ronald P. , Kleinman Steven M. , Ashkenazi Tzachi
Published: February 2023

The last thirty years has seen a transformation in deception research from passively observing subjects’ nonverbal behavior to actively interviewing subjects to elicit verbal cues to deceit. Although significant progress has been made, there is still much work to do in the rapidly developing field of verbal lie detection. In this contribution, we briefly discuss the current status of the field. We outline the four interview protocols most frequently discussed in the scientific literature to date—Assessment Criteria Indicative of Deception (ACID), Cognitive Credibility Assessment (CCA), Strategic Use of Evidence (SUE), and Verifiability Approach (VA)—followed by the empirical support for these protocols. We then present ideas on how to move the field of verbal lie detection forward.
Human Factors in Forensic Science
Authors: Kukucka Jeff , Dror Itiel E.
Published: February 2023

Forensic science evidence has long been accepted in court and is widely considered infallible. However, the forensic sciences have recently come under intense scrutiny, as forensic science errors have been implicated in an alarming number of wrongful convictions. In working to better understand and prevent such errors, researchers have discovered that they are often an unfortunate by-product of innate psychological processes. This chapter first reviews evidence that forensic science examiners, like all humans, are vulnerable to unconscious biases that can lead to erroneous judgments. Second, the chapter identifies barriers to mitigating the pernicious effects of bias in forensic laboratories and courtrooms, including widespread misconceptions about its causes and effects. Third, proposed reforms are offered to strengthen forensic science, with descriptions of some progress that has already been made in that regard.
Metaphor, Myth, and Symbol in the Grain of Time
Authors: Sinha Chris
Published: February 2023

This chapter begins by analyzing metaphoric and spatialized conceptualizations of time in theories of human social evolution, from the late eighteenth and early nineteenth century onwards. The situatedness in European imperial conquest of the concept of social progress, as well as the denial of coevalness to non-Western peoples, is emphasized. The projection of this conceptual “phylocultural complex” onto early human evolution is described, as well as the reaction against it from the early twentieth century onwards. The roots of deterministic narratives of “agriculture as destiny” in nineteenth century anthropology are explored, and the contemporary counter-narrative of the “return of coevalness” is described in relation to co-evolutionary theories of hominin evolution, the social systems of historic human societies, and the impact of colonization on indigenous non-Western societies. The chapter concludes by summarizing the evidence for a “globalization of time” in the late sixteenth and early seventeenth centuries, set in train by the European conquest of the Americas, and ushering in the Anthropocene epoch.
Digital Culture
Authors: Acerbi Alberto
Published: February 2023

The diffusion of digital technologies triggered a radical departure from previous modalities of cultural transmission but, at the same time, general characteristics of human cultural evolution and cognition influence these developments. This chapter explores some areas where the contacts between cultural evolution research and digital media seem promising. As cultural evolution-inspired research on Internet phenomena is still limited, these areas represent suggestions and links with works in other disciplines more than reviews of past research in cultural evolution. These include topics such as how to conceptualize social influence online and how information spreads in social media; how digital media could enhance cumulative culture; and the differences between online and offline cultural transmission. The chapter will then briefly consider possible future directions: the influence of different affordances in different media supporting cultural transmission; the role of producers of cultural traits; and, finally, the effects on cultural dynamics of algorithms selecting information.
Teaching with Technology
Authors: Wiley Korah , Gerard Libby , Bradford Allison , Linn Marcia C.
Published: February 2023

This chapter synthesizes the role of technology in empowering teachers to enact responsive science curriculum that respects the ideas and expertise of each student. Open educational resources such as authoring and customizing environments capture and display student progress in ways that support teachers in customizing instruction in response to students’ learning needs. Furthermore, advances in natural language processing technology allow teachers to rapidly assess students’ understanding of complex science ideas. When combined with learning analytics dashboards, these technologies can support teachers in affirming students’ efforts to make sense of science. This chapter highlights the value of collaborative partnerships between educational researchers, system developers, and teachers for learning how to leverage technology to build students’ agency and identity as science learners.
Armadillo repeat only protein GS10 negatively regulates brassinosteroid signaling to control rice grain size
Authors: Chen Erwang , Hou Qingqing , Liu Kun , Gu Zhoulin , Dai Bingxin , Wang Ahong , Feng Qi , Zhao Yan , Zhou Congcong , Zhu Jingjie , Shangguan Yingying , Wang Yongchun , Lv Danfeng , Fan Danlin , Huang Tao , Wang Zixuan , Huang Xuehui , Han Bin
Published: February 2023

Grain yield and grain quality are major determinants in modern breeding controlled by many quantitative traits loci (QTLs) in rice (Oryza sativa). However, the mechanisms underlying grain shape and quality are poorly understood. Here, we characterize a QTL for grain size and grain quality via map-based cloning from wild rice (W1943), GS10 (Grain Size on Chromosome 10), which encodes a protein with 6 tandem armadillo repeats. The null mutant gs10 shows slender and narrow grains with altered cell size, which has a pleiotropic effect on other agronomical traits. Functional analysis reveals that GS10 interacts with TUD1 (Taihu Dwarf1) and is epistatic to OsGSK2 (glycogen synthase kinase 2) through regulating grain shape and lamina joint inclination, indicating it is negatively involved in brassinosteroid (BR) signaling. Pyramiding gs10 and the grain size gene GW5 into cultivar GLA4 substantially improved grain shape and appearance quality. Natural variation analysis revealed that gs10 from the wild rice Oryza rufipogon W1943 is a rare allele across the rice population. Collectively, these findings advance our understanding of the underlying mechanism of grain shape and provide the beneficial allele of gs10 for future rice breeding and genetic improvement.
Abscisic acid and regulation of the sugar transporter gene MdSWEET9b promote apple sugar accumulation
Authors: Zhang Shuhui , Wang Hui , Wang Tong , Zhang Jing , Liu Wenjun , Fang Hongcheng , Zhang Zongying , Peng Futian , Chen Xuesen , Wang Nan
Published: February 2023

Enhancing fruit sugar contents, especially for high-flavonoid apples with a sour taste, is one of the main goals of horticultural crop breeders. This study analyzed sugar accumulation and the underlying mechanisms in the F2 progenies of a hybridization between the high-sugar apple (Malus × domestica) variety “Gala” and high-flavonoid apple germplasm “CSR6R6”. We revealed that MdSWEET9b (sugars will eventually be exported transporter) helps mediate sugar accumulation in fruits. Functional characterization of MdSWEET9b in yeast mutants lacking sugar transport as well as in overexpressing and CRISPR/Cas9 knockdown apple calli revealed MdSWEET9b could transport sucrose specifically, ultimately promoting normal yeast growth and accumulation of total sugar contents. Moreover, MdWRKY9 bound to the MdSWEET9b promoter and regulated its activity, which responded to abscisic acid (ABA) signaling. Furthermore, MdWRKY9 interacted with MdbZIP23 (basic leucine zipper) and MdbZIP46, key ABA signal transducers, at the protein and DNA levels to enhance its regulatory effect on MdSWEET9b expression, thereby influencing sugar accumulation. Based on the contents of ABA in lines with differing sugar contents and the effects of ABA treatments on fruits and calli, we revealed ABA as one of the main factors responsible for the diversity in apple fruit sugar content. The results of this study have clarified how MdSWEET9b influences fruit sugar accumulation, while also further elucidating the regulatory effects of the ABA-signaling network on fruit sugar accumulation. This work provides a basis for future explorations of the crosstalk between hormone and sugar metabolism pathways.
MEDIATOR SUBUNIT 16 negatively regulates rice immunity by modulating PATHOGENESIS RELATED 3 activity
Authors: Zhang Peng , Ma Xiaoding , Liu Lina , Mao Chanjuan , Hu Yongkang , Yan Bingxiao , Guo Jia , Liu Xinyu , Shi Jinxia , Lee Gang-Seob , Pan Xiaowu , Deng Yiwen , Zhang Zhengguang , Kang Zhensheng , Qiao Yongli
Published: February 2023

Lesion mimic mutants (LMMs) are valuable genetic resources for unraveling plant defense responses including programmed cell death. Here, we identified a rice (Oryza sativa) LMM, spotted leaf 38 (spl38), and demonstrated that spl38 is essential for the formation of hypersensitive response-like lesions and innate immunity. Map-based cloning revealed that SPL38 encodes MEDIATOR SUBUNIT 16 (OsMED16). The spl38 mutant showed enhanced resistance to rice pathogens Magnaporthe oryzae and Xanthomonas oryzae pv. oryzae (Xoo) and exhibited delayed flowering, while OsMED16-overexpressing plants showed increased rice susceptibility to M. oryzae. The OsMED16-edited rice lines were phenotypically similar to the spl38 mutant but were extremely weak, exhibited growth retardation, and eventually died. The C-terminus of OsMED16 showed interaction with the positive immune regulator PATHOGENESIS RELATED 3 (OsPR3), resulting in the competitive repression of its chitinase and chitin-binding activities. Furthermore, the ospr3 osmed16 double mutants did not exhibit the lesion mimic phenotype of the spl38 mutant. Strikingly, OsMED16 exhibited an opposite function in plant defense relative to that of Arabidopsis (Arabidopsis thaliana) AtMED16, most likely because of 2 amino acid substitutions between the monocot and dicot MED16s tested. Collectively, our findings suggest that OsMED16 negatively regulates cell death and immunity in rice, probably via the OsPR3-mediated chitin signaling pathway.
“Doing what others do” does not stabilize continuous norms
Authors: Yan Minhua , Mathew Sarah , Boyd Robert
Published: February 2023

Differences in social norms are a key source of behavioral variation among human populations. It is widely assumed that a vast range of behaviors, even deleterious ones, can persist as long as they are locally common because deviants suffer coordination failures and social sanctions. Previous models have confirmed this intuition, showing that different populations may exhibit different norms even if they face similar environmental pressures or are linked by migration. Crucially, these studies have modeled norms as having a few discrete variants. Many norms, however, have a continuous range of variants. Here we present a mathematical model of the evolutionary dynamics of continuously varying norms and show that when the social payoffs of the behavioral options vary continuously the pressure to do what others do does not result in multiple stable equilibria. Instead, factors such as environmental pressure, individual preferences, moral beliefs, and cognitive attractors determine the outcome even if their effects are weak, and absent such factors populations linked by migration converge to the same norm. The results suggest that the content of norms across human societies is less arbitrary or historically constrained than previously assumed. Instead, there is greater scope for norms to evolve towards optimal individual or group-level solutions. Our findings also suggest that cooperative norms such as those that increase contributions to public goods might require evolved moral preferences, and not just social sanctions on deviants, to be stable.
Gender differences in vascular aging and in coronary artery disease pathophysiology
Authors: Blum A
Published: February 2023

Women have a clinical advantage over men in relation to atherosclerotic cardiovascular disease (CVD) (morbidity and mortality). This advantage disappears once women become older, and in their seventh decade, the risk to develop CVD equals men at that age. There have been several theories about this gender difference that were related to hormones, and the different morphology and physiology that characterize the cardiovascular system in women. In this review, the different mechanisms will be reviewed and discussed.
On the societal impact of publicly funded Circular Bioeconomy research in Europe
Authors: Brandão Ana Sofia , Santos José M R C A
Published: February 2023

Europe has taken a world leadership position in setting policy priorities for Circular Bioeconomy (CBE) as a key determinant of economic, social, and environmental sustainability. Consequently, European R&D investment in this area keeps growing along with the societal pressure to demonstrate the return of investment of publicly funded projects. Thus, this work presents a pioneering exploratory analysis of the extent to which projects funded at the European level incorporate the policy priorities for which they are being designed in the context of CBE, and how can the impact they are having on society be assessed. Thence, project impact evaluation is carried out in the short- and medium-term, and categorized under Industrial Competitiveness, Sustainable Development, and Community and Public Policies. For this purpose, secondary information was gathered from the European projects database Cordis, as well as primary information through a questionnaire survey of project coordinators. The empirical data collected suggest that European Framework Programmes have been fulfilling their purpose, as they are increasingly societal challenges-driven and market-oriented. This is evidenced by market-related topics addressed in the projects analysed and by the active participation of companies that outnumber academic institutions. As far as impact is concerned, scientific publications continue to be the main result of this type of project in the short-term, whereas in the medium-term social and economic benefits were also identified. Notably, the creation of scientific jobs in the industry, of industrial joint ventures, and the generation of documents to support the improvement of public and EU policies on biobased products.
Genicular nerve radiofrequency ablation
Authors: Swanson Jennifer L.
Published: February 2023

Genicular nerve radiofrequency ablation is an option to treat osteoarthritic knee pain unresponsive to conservative and minimally invasive measures. This article reviews genicular nerve radiofrequency ablation, neuroanatomy of the knee, patient selection, results, and risks and complications of the procedure.
PAs and NPs in employee health during the COVID-19 pandemic
Authors: O'Bryan Pauline , Cutrell James , Gonzalez John D. , Namiranian Azadeh
Published: February 2023

COVID-19 created unprecedented occupational health challenges for hospitals. To meet these demands at a large county safety-net hospital, a COVID-19 employee response team led by PAs and NPs was created. From April 2020 through February 2022, this team managed more than 14,000 discrete employee contacts related to COVID-19 employee concerns. This article describes our experience in creating this team and highlights key strengths and lessons for other institutions seeking to adopt similar models.
Are beta-blockers safe and effective after myocardial infarction in patients with COPD?
Authors: Davis Lindsay E. , Pogge Elizabeth K. , Garg Rajeev
Published: February 2023

Clinicians may be hesitant to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) who have a comorbid compelling cardiovascular indication for beta-blocker therapy. This article summarizes the available data on the safety and efficacy of beta-blockers in patients with COPD and recent myocardial infarction.
Illicit Drugs May Contain Veterinary Tranquilizer
Authors: Aschenbrenner Diane S.
Published: February 2023

There has been a rise in illicit drugs such as fentanyl being mixed with xylazine, a veterinary tranquilizer. Xylazine is not an opioid; although opioids and xylazine induce similar respiratory symptoms, naloxone will not reverse a xylazine overdose. Severe necrotic skin ulcerations are also possible from frequent exposure to xylazine.

Nurses who encounter patients with severe necrotic skin ulcerations or respiratory symptoms should consider xylazine overdose and attempt to determine if xylazine abuse is the root cause.
Wood dust and asthma
Authors: Baatjies Roslynn , Chamba Paulino , Jeebhay Mohamed F.
Published: February 2023

Purpose of the review

Review recent developments on asthma associated with wood dust, given the increasing scale of wood handling and processing activities globally.

Recent findings

Work in wood industries is associated with a significantly increased risk of respiratory symptoms, rhinitis and asthma. This can be attributed to traditional processing techniques and newer technologies producing complex bioaerosol exposures, which may include chemicals. Meta-analysis studies indicate strong evidence for wood dusts as occupational sensitizers for asthma, but the underlying mechanisms remain poorly understood. The global prevalence of asthma in wood workers ranges between 6–18% and for rhinitis 16–33%. Exposure estimates show wide variation. Risk factors include atopy and exposure to certain wood species, elevated current and cumulative particulate exposures.

Future studies should focus on better characterization of wood dust allergens and other bioaerosol components, specific immunoglobulin E responses to different wood species, pathophysiological mechanisms underlying asthma, and modelling dose–response relationships using refined exposure metrics for dust particulate and other bioaerosol components. There is a need for improved health-based international exposure standards and effective workplace control measures to reduce exposures to wood dust particulate (hard and soft woods), endotoxin and β-glucan, to reduce the risks of asthma in wood workers.
E-cigarettes and asthma in adolescents
Authors: Afolabi Folashade , Rao Devika R.
Published: February 2023

Purpose of review

E-cigarettes have been long purported to be a mechanism of harm reduction in current smokers. However, market expansion to adolescents has been aggressive, despite government interventions. Research examining the adverse effects of e-cigarettes in teens with asthma has been limited. We discuss the most recent data on the pulmonary manifestations of e-cigarettes use and exposure in adolescents with asthma.

Recent findings

Adolescents with asthma are more likely to be e-cigarette users than those without asthma and more likely to have asthma exacerbations. Increased pulmonary inflammatory cytokines have been seen in e-cigarette users and mouse models. Yet, providers are not confident in e-cigarette screening and counselling despite acknowledging adolescents are using e-cigarettes regularly.

Since the introduction of e-cigarettes into the United States market in 2007, adolescents use of these products has risen, even after a brief decline during the height of the COVID-19 pandemic. This review will describe the most recent studies on e-cigarette use trends, cytotoxicity of e-cigarette aerosol and associations with the diagnosis and symptoms of asthma. Knowledge gaps, advocacy efforts, evidence on e-cigarette cessation will be highlighted.
Management of Very Distal Ulna Fractures: A Systematic Review
Authors: Abdel Khalik Hassaan , Lameire Darius L. , Kruse Colin , Hache Philip J. , Al-Asiri Jamal
Published: February 2023

Objectives:

To synthesize all-cause complications and reoperations data, and secondary clinical, functional, and radiographic outcomes after the management of very distal ulna fractures (VDUFs) either nonoperatively or operatively.

Data Sources:

MEDLINE, Embase, and Web of Science were searched for English-language articles from inception to February 17, 2022.

Study Selection:

Studies reporting the nonoperative or operative management of VDUFs were eligible for inclusion. VDUFs were defined as either being Q2–Q5 distal ulna fractures using the OTA/AO Comprehensive Classification of Fractures for distal ulna fractures associated with distal radius fractures or being amenable to characterization by the classification system for ulnar head, neck and metaphyseal fractures by Biyani et al.

Data Extraction:

Two reviewers independently extracted data from included studies. Study validity was assessed using the methodological index for nonrandomized studies.

Data Synthesis:

Seventeen studies (512 VDUFs) were included for analysis. There were 209, 237, and 66 fractures in the nonoperative, open reduction internal fixation (ORIF), and distal ulna resection groups, respectively. Descriptive statistics including weighted mean values, standard deviations, and 95% confidence intervals were calculated.

Conclusions:

The treatment of VDUFs with nonoperative management, ORIF, or distal ulna resection may all be acceptable treatment options in specific patient populations. Nonoperative management of VDUFs is a promising treatment strategy even for complex fracture patterns in patients 65 years of age or older. Despite higher reoperation rates, ORIF may be considered for the younger, high-demand patient. Distal ulna resection presents with very favorable functional outcomes in patients 65 years of age or older presenting with a complex VDUF with the lowest reoperation rate across all groups.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Impact of the Magnitude and Timing of Fluid Overload on Outcomes in Critically Ill Children: A Report From the Multicenter International Assessment of Worldwide Acute Kidney Injury, Renal Angina, and Epidemiology (AWARE) Study
Authors: Selewski David T. , Gist Katja M. , Basu Rajit K. , Goldstein Stuart L. , Zappitelli Michael , Soranno Danielle E. , Mammen Cherry , Sutherland Scott M. , Askenazi David J. , Ricci Zaccaria , Akcan-Arikan Ayse , Gorga Stephen M. , Gillespie Scott E. , Woroniecki Robert ,   on behalf of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) Investigators
Published: February 2023

OBJECTIVES:

With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes.

DESIGN:

Prospective cohort study.

SETTING:

Multicenter, international collaborative of 32 pediatric ICUs.

PATIENTS:

A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [n = 1753], FO ≥ 10%Day1 in 11.7% [n = 537], FO ≥ 5%Day2 in 53.3% [n = 1,539], FO ≥ 10%Day2 in 25.1% [n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days.

CONCLUSIONS:

This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.
Avelumab in Men With Metastatic Castration-Resistant Prostate Cancer, Enriched for Patients Treated Previously With a Therapeutic Cancer Vaccine
Authors: Madan Ravi A. , Redman Jason M. , Karzai Fatima , Dahut William L. , Cordes Lisa , Fakhrejahani Farhad , Vu Tuyen , Sheikh Nadeem , Schlom Jeffrey , Gulley James L.
Published: February 2023

Therapeutic cancer vaccines including sipuleucel-T, a prostatic acid phosphatase (PAP) targeted vaccine that improves survival in metastatic castration-resistant prostate cancer (mCRPC), can produce immune responses that translate to clinical benefit. The effects of sequential checkpoint inhibitors after therapeutic vaccine on immune responses are unknown. Avelumab is an anti–programmed death ligand-1 monoclonal antibody evaluated in patients with mCRPC in the JAVELIN solid tumor phase 1 trial expansion cohort, enriched for patients with a previous therapeutic prostate cancer-targeted vaccine. mCRPC patients received intravenous avelumab 10 mg/kg every 2 weeks with imaging every 6 weeks. Peripheral blood T-cell responses to PAP and to PA2024, the peptide containing PAP utilized by the vaccine, were evaluated pre and posttreatment. Eighteen patients enrolled, and previous treatments included abiraterone or enzalutamide in 14 (78%), therapeutic cancer vaccine in 14 (78%), and chemotherapy in 4 (22%). Avelumab had a manageable safety profile. There were no sustained prostate specific antigen decreases. Of 17 patients evaluable for best overall response by RECISTv1.1, 12 had stable disease (SD) and 5 had progressive disease. Seven patients had SD for >24 weeks posttreatment. Fourteen patients had previously received therapeutic cancer vaccines. Eleven (79%) had SD as the best overall response. Of these 14 patients, 9 had previously received sipuleucelT. Analysis of antigen-specific T-cell responses pre and postavelumab treatment did not demonstrate changes in interferon-γ production or proliferation in response to PAP or PA2024. This unplanned analysis does not support the use of sequential therapeutic cancer vaccine therapy followed by programmed death ligand-1 inhibition in mCRPC.
Neurosensory Re-education following Gender-affirming Phalloplasty: A Novel Treatment Protocol
Authors: Peters Blair R. , Annen Alvin A. , Berli Jens U. , Gallagher Sandra , Smigelski Caitlin , Kahn Lorna H. , Skelton Hales E.
Published: February 2023

Background:

Sensory nerve transfers are performed as part of phalloplasty surgery. Despite this, sensory re-education to rehabilitate these nerve transfers has not been employed. Additionally, little attention has been paid to the role of the central nervous system in experienced sensation following phalloplasty. The purpose of this article is to report on the development of a targeted rehabilitation protocol to integrate and optimize peripheral and central contributions to sensation following phalloplasty.

Methods:

This neurosensory re-education protocol was constructed over four phases by a multi-disciplinary team (phalloplasty/peripheral nerve surgeon, reconstructive urologist, pelvic floor physiotherapists, nerve therapist, sex therapist, sexual medicine physician) and individuals with lived phalloplasty experience. The final protocol was approved by all team members and is supported here by qualitative narratives from people with lived phalloplasty experience.

Results:

The protocol is built to follow each stage of phalloplasty surgery. In each stage, exercises are grouped into three core themes: visualization, tactile stimulation, and sexual/erogenous stimulation. Visualization exercises progress from static to dynamic. Tactile exercises start at simple touch and progress toward targeted sensory stimulation. Sexual stimulation focuses on developing erogenous sensation in the phallus that is separate from erogenous sensation in the natal clitoral tissue. By recommendation of individuals with phalloplasty, the protocol is now integrated into our center’s phalloplasty care pathway for all individuals undergoing phalloplasty surgery.

Conclusion:

We introduce a novel protocol targeting peripheral and central contributions to sensation to provide a tool to help optimize experienced sensation for transmasculine individuals undergoing phalloplasty.
Threatened Ventricular Assist Devices: Meta-analysis of Negative Pressure Therapy and Flap Reconstruction Outcomes
Authors: Clark Robert C. , Swanson Marco A. , Cai Yida , Sarode Anuja L. , Lineberry Kyle D. , Kumar Anand R.
Published: February 2023

Background:

Infected Ventricular Assist Device (VAD)–associated wounds are common and associated with significant morbidity and mortality. The efficacy of hardware salvage utilizing flaps and negative pressure wound therapy (NPWT) remains understudied. We hypothesized that patients treated with flaps and/or NPWT would have higher hardware salvage rates compared with other surgical management strategies.

Methods:

A meta-analysis study evaluating VAD-associated wounds was performed following PRISMA guidelines. Primary predictor variables were flap-reconstruction (FR), NPWT, no FR, and infection location (mediastinum versus driveline). Primary outcomes were hardware retention (salvage) versus explantation, infection recurrence, or death. Twenty-nine studies were included. Standard statistical methods included logistic regression analysis.

Results:

Seventy-four subjects with nonsignificant demographic differences between cohorts were identified. Overall salvage was 59.5% in both driveline and mediastinum cohorts. Overall, NPWT significantly improved salvage compared with no NPWT [77.4% versus 46.5% respectively (P = 0.009)], and FR significantly improved salvage compared with no FR [68.6% versus 39.1% respectively (P = 0.022)]. Logistic regression analysis predicting odds of salvage by FR (area under curve = 0.631) was significantly three times higher (95% CI: 1.2–9.5) and predicting the odds for salvage by NPWT (area under curve = 0.656) was significantly four times higher (95% CI: 1.4–11.1) compared with other treatment.

Conclusions:

NPWT or flap reconstruction for treatment of threatened VAD hardware was associated with a significantly improved device salvage compared with other surgical strategies. Further study should focus on subgroup analysis of flaps utilized and synergistic treatment benefits.
κ-Opioid Receptor Plasma Levels Are Associated With Sex and Diagnosis of Major Depressive Disorder But Not Response to Ketamine
Authors: Quintanilla Brandi , Medeiros Gustavo C. , Greenstein Dede , Yuan Peixiong , Johnston Jenessa N. , Park Lawrence T. , Goes Fernando S. , Gould Todd D. , Zarate Carlos A.
Published: February 2023

Background

Preclinical evidence indicates that the κ-opioid receptor (KOR)/dynorphin pathway is implicated in depressive-like behaviors. Ketamine is believed to partly exert its antidepressant effects by modulating the opioid system. This post hoc study examined the following research questions: (1) at baseline, were there differences in KOR or dynorphin plasma levels between individuals with major depressive disorder (MDD) and healthy volunteers (HVs) or between men and women? (2) in individuals with MDD, did KOR or dynorphin baseline plasma levels moderate ketamine's therapeutic effects or adverse effects? and (3) in individuals with MDD, were KOR or dynorphin plasma levels affected after treatment with ketamine compared with placebo?

Methods

Thirty-nine unmedicated individuals with MDD (23 women) and 25 HVs (16 women) received intravenous ketamine (0.5 mg/kg) and placebo in a randomized, crossover, double-blind trial. Blood was obtained from all participants at baseline and at 3 postinfusion time points (230 minutes, day 1, day 3). Linear mixed model regressions were used.

Results

At baseline, participants with MDD had lower KOR plasma levels than HVs (F
1,60 = 13.16, P < 0.001), and women (MDD and HVs) had higher KOR plasma levels than men (F
1,60 = 4.98, P = 0.03). Diagnosis and sex had no significant effects on baseline dynorphin levels. Baseline KOR and dynorphin levels did not moderate ketamine's therapeutic or adverse effects. Compared with placebo, ketamine was not associated with postinfusion changes in KOR or dynorphin levels.

Conclusions

In humans, diagnosis of MDD and biological sex are involved with changes in components of the KOR/dynorphin pathway. Neither KOR nor dynorphin levels consistently moderated ketamine's therapeutic effects or adverse effects, nor were levels altered after ketamine infusion.

Trial Registration

NCT00088699 (ClinicalTrials.gov).
Impact of COVID-19 Pandemic on Human Papillomavirus Vaccine Uptake in Israel
Authors: Lavie Michael , Lavie Inbar , Laskov Ido , Cohen Aviad , Grisaru Dan , Grisaru-Soen Galia , Michaan Nadav
Published: February 2023

Objective

Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic.

Methods

The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020–2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure.

Results

The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel (p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia.

Conclusions

Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge “vaccination gaps” that may be caused by future pandemics.
Nutrition and diet in inflammatory bowel disease
Authors: Yamamoto Takayuki , Shimoyama Takahiro
Published: February 2023

Purpose of review

This study was to review the current evidence for dietary risk factors for developing inflammatory bowel disease (IBD), and therapeutic benefit of dietary and enteral interventions in IBD.

Recent findings

A Westernized diet rich in protein, fats and refined carbohydrates and low in fibre, fruits and vegetables may increase risk of developing IBD. Nevertheless, there are methodological limitations in case–control studies, which can affect the accuracy of the outcomes. Currently, various dietary interventions and supplements have been attempted to control the disease activity of IBD, but none of them showed striking efficacy. Exclusive enteral nutrition (EEN) is recommended as the first-line therapy in paediatric patients with active Crohn's disease. EEN is recommended in adults with good adherence to enteral formula and with intolerance to corticosteroids. Partial enteral nutrition is not recommended as primary therapy for the maintenance of remission, but it is used when undernutrition cannot be treated sufficiently with diets.

Dietary risk factors for IBD, and the efficacies of dietary and enteral interventions need to be confirmed by large, well designed studies.
Carnitine derivatives beyond fatigue: an update
Authors: Malaguarnera Michele , Catania Vito Emanuele , Malaguarnera Mariano
Published: February 2023

Purpose of review

Carnitine is an essential micronutrient that transfer long-chain fatty acids from the cytoplasm into the mitochondrial matrix for the β-oxidation. Carnitine is also needed for the mitochondrial efflux of acyl groups in the cases wherein substrate oxidation exceeds energy demands.

Recent findings

Carnitine deficiency can affect the oxidation of free fatty acids in the mitochondria resulting in the aggregation of lipids in the cytoplasm instead of entering the citric acid cycle. The aggregation leads a lack of energy, acetyl coenzyme A accumulation in the mitochondria and cytotoxic production.

Carnitine and its derivatives show great clinical therapeutic effect without significant side effects.
Elevations in End-Tidal CO2 With CO2 Use During Pediatric Endoscopy With Airway Protection: Is This Physiologically Significant?
Authors: Dike Chinenye R. , Huang Pacheco Andrew , Lyden Elizabeth , Freestone David , Choudhry Ojasvini , Bishop Warren P. , Shukry Mohanad
Published: February 2023

Background:

Inflation of the gastrointestinal lumen is vital for proper visualization during endoscopy. Air, insufflated via the endoscope, is gradually being replaced with carbon dioxide (CO2) in many centers, with the intention of minimizing post-procedural discomfort due to retained gas. Recent studies suggest that the use of CO2 during pediatric esophagogastroduodenoscopy (EGD) with an unprotected airway is associated with transient elevations in exhaled CO2 (end-tidal CO2, EtCO2), raising safety concerns. One possible explanation for these events is eructation of insufflation gas from the stomach.

Objectives:

To distinguish eructated versus absorbed CO2 by sampling EtCO2 from a protected airway with either laryngeal mask airway (LMA) or endotracheal tube (ETT), and to observe for changes in minute ventilation (MV) to exclude hypoventilation events.

Methods:

Double-blinded, randomized clinical trial of CO2 versus air insufflation for EGD with airway protection by either LMA or ETT. Tidal volume, respiratory rate, MV, and EtCO2 were automatically recorded every minute. Cohort demographics were described with descriptive characteristics. Variables including the percent of children with peak, transient EtCO2 ≥ 60 mmHg were compared between groups.

Results:

One hundred ninety-five patients were enrolled for 200 procedures. Transient elevations in EtCO2 of ≥60 mmHg were more common in the CO2 group, compared to the air group (16% vs 5%, P = 0.02), but were mostly observed with LMA and less with ETT. Post-procedure pain was not different between groups, but flatulence was reported more with air insufflation (P = 0.004).

Conclusion:

Transient elevations in EtCO2 occur more often with CO2 than with air insufflation during pediatric EGD despite protecting the airway with an LMA or, to a lesser degree, with ETT. These elevations were not associated with changes in MV. Although no adverse clinical effects from CO2 absorption were observed, these findings suggest that caution should be exercised when considering the use of CO2 insufflation, especially since the observed benefits of using this gas were minimal.
Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas
Authors: Ishimoto-Namiki Utako , Ino Yoshinori , Esaki Minoru , Shimada Kazuaki , Saruta Masayuki , Hiraoka Nobuyoshi
Published: February 2023

Acinar cell carcinoma (ACC) is a rare and highly malignant pancreatic tumor. Owing to histologic similarity, ACC is often difficult to distinguish from other solid medullary pancreatic tumors, particularly neuroendocrine neoplasm (NEN) and intraductal tubulopapillary neoplasm (ITPN). We aimed to identify new immunohistochemical markers commonly expressed in tumor cells with acinar cell differentiation and useful for both surgical and small biopsy specimens. Candidate molecules exclusively expressed in neoplastic or non-neoplastic acinar cells in pancreatic tissues with specific and available antibodies suitable for immunohistochemistry were selected. We selected carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and glycoprotein 2 (GP2), which were expressed in 100%, 100%, and 96% of cases, respectively, in ACC (n=27) or neoplasia with acinar cell differentiation, including mixed acinar-neuroendocrine carcinoma (n=9), mixed acinar-ductal carcinoma (n=3), pancreatoblastoma (n=4), and acinar cystic transformation (n=2), in the cytoplasm of tumor cells with a granular pattern. Both CPA2 and CPA1 were not expressed in any other tumors without acinar cell differentiation, including NEN (n=44), pancreatic ductal adenocarcinoma (n=44), and ITPN (n=4). GP2 was not expressed in these tumors except in rare cases, including 14% of NEN, 15% of intraductal papillary-mucinous neoplasm, 25% of intraductal oncocytic papillary neoplasm, 25% of ITPN, and 7% of pancreatic ductal adenocarcinoma, wherein a small proportion of tumor cells expressed GP2 in their apical cell membrane. NEN cases also showed cytoplasmic GP2 expression. Therefore, CPA2, CPA1, and potentially GP2 may act as ACC markers.
Adverse Events During Apnea Testing for the Determination of Death by Neurologic Criteria: A Single-Center, Retrospective Pediatric Cohort*
Authors: Sveen William N. , Antommaria Armand H. Matheny , Gilene Stephen J. , Stalets Erika L.
Published: February 2023

OBJECTIVES:

To report the prevalence of adverse events in children undergoing apnea testing as part of the determination of death by neurologic criteria (DNC).

DESIGN:

Single-center, retrospective study.

SETTING:

Academic children’s hospital that is a Level I Trauma Center.

PATIENTS:

All children who underwent apnea testing to determine DNC from July 2013 to June 2020.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We abstracted the medical history, blood gases, ventilator settings, blood pressures, vasoactive infusions, intracranial pressures, chest radiographs, and echocardiograms for all apnea tests as well as any ancillary test. Adverse events were defined as hypotension, hypoxia, pneumothorax, arrhythmia, intracranial hypertension, and cardiac arrest. Fifty-eight patients had 105 apnea tests. Adverse events occurred in 21 of 105 apnea tests (20%), the most common being hypotension (15/105 [14%]) and hypoxia (4/105 [4%]). Five of 21 apnea tests (24%) with adverse events were terminated prematurely (three for hypoxia, one for hypotension, and one for both hypoxia and hypotension) but the patients did not require persistent escalation in care. In the other 16 of 21 apnea tests (76%) with adverse events, clinical changes were transient and managed by titrating vasoactive infusions or completing the apnea test.

CONCLUSIONS:

In our center, 20% of all apnea tests were associated with adverse events. Only 5% of all apnea tests required premature termination and the remaining 15% were completed and the adverse events resolved with medical care.