bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroimaging and Circuit Mechanisms of Anxiety and Trauma-Related Disorders
Authors: Fonzo Gregory A.
Published: January 2025

Functional neuroimaging of anxiety and trauma-related disorders has substantially enhanced neurobiological understanding of these conditions in humans. This chapter summarizes neuroimaging studies examining emotional reactivity, defensive learning, and emotion regulation in anxiety and trauma-related disorders. Across diagnoses, anxiety is characterized by not only a propensity toward facilitated fear learning and deficient ability to overwrite this learning but also elevated reactivity to threatening and emotionally provocative cues and difficulty adaptively regulating emotional states. These processes generally implicate elevated activity in defensive threat circuitry. However, specific diagnoses differ in the stimuli eliciting such responses and the relative predominance of each component to the neural phenotype. This chapter synthesizes a conceptual and neurobiological framework through which existing findings can be contextualized. This framework highlights abnormal limbic and prefrontal function during response to, learning about, and regulation of emotion-eliciting stimuli as a unifying construct for understanding the neurobiology of anxiety and trauma-related disorders.
Biological Mechanisms of Anxiety Disorders
Authors: Gerhard Danielle M. , Anfei Li , Lee Francis S. , Meyer Heidi C.
Published: January 2025

Abstract: Anxiety disorders are characterized by persistent and debilitating feelings of worry stemming from difficulty assessing threats and inhibiting fear responding. However, heterogeneity of symptom profiles across anxiety disorders, and even within the same diagnoses, has complicated treatment because treatment success varies widely across patients. Improved mechanistic understanding of the disparate symptoms of anxiety disorders is needed to help inform the development of new treatments. There is a growing understanding that psychiatric disease, including anxiety disorders, results from perturbation of key brain regions and their complex local and regional circuitries. Increasing attention has also been given to the influence of specific genetic polymorphisms and their effects on circuit activity and behavior. This chapter highlights human neuroimaging and rodent studies that parallel one another and illustrate how an integrated approach has advanced understanding of neural circuits implicated in anxiety disorders.
Biological Mechanisms of Stress Resilience
Authors: Seeley Saren H. , Boukezzi Sarah , DePierro Jonathan , Charney Dennis S. , Feder Adriana
Published: January 2025

Abstract: Resilience is the ability to adapt successfully in the face of severe stress, trauma, or adversity. Best conceptualized as existing on a continuum, resilience is shaped by genetic makeup and environmental factors. The developmental years are critical for the shaping of stress response systems and brain circuits underlying emotion regulation, yet resilience can also be enhanced throughout an individual’s lifetime. This chapter presents an overview of the complex interactions between neurotransmitters, neuropeptides, hormones, and other biological systems that mediate stress resilience, as well as functional differences in neural circuitry function underlying key resilience-promoting psychological factors. The growing understanding of genetic, epigenetic, developmental, psychological, and neurobiological resilience factors continues to lead to the development of interventions to enhance stress resilience. Examples of preventive and treatment interventions are discussed, along with recent developments in the field.
Novel Approaches for Treating Substance Use Disorders
Authors: Banks Matthew L.
Published: January 2025

Clinical substance use disorder (SUD) treatment goals are to not only decrease drug-taking behavior but also promote allocation of behavior toward nondrug reinforcers. Preclinical drug self-administration procedures have demonstrated utility in candidate SUD medication evaluation. Decades of research has validated experimental design attributes that facilitate translation of preclinical-to-clinical results when evaluating candidate therapeutic effects. These experimental design considerations include repeated candidate therapeutic treatment to model clinical chronic dosing regimens, candidate therapeutic evaluation on self-administered abused drug dose–effect functions, and assessment of behavioral selectivity for drug- versus nondrug-maintained behaviors. Sophisticated drug “choice” self-administration procedures allow for a simplified assessment of these clinical treatment goals in a preclinical setting while also incorporating assessment of behavioral selectivity. The infrequent incorporation of these rigorous experimental design attributes has hindered preclinical SUD medication development research efforts. Future directions include the inclusion of active negative control comparator treatments to facilitate interpretation of candidate medication effects.
Current Treatments for Alzheimer’s Disease
Authors: Sano Mary , Neugroschl Judith
Published: January 2025

In 2023, the U.S. Food and Drug Administration (FDA) fully approved the first drug for the treatment of Alzheimer’s disease that targeted amyloid accumulation in the brain and provided evidence of clinical benefit. This chapter describes the approach that led to new drugs that are potentially disease modifying. Drug treatments provide symptomatic benefit to patients with Alzheimer’s disease and related dementias (ADRD) are also described. Up-to-date data that continue to support their use are reviewed. Effective mechanisms for managing cardiovascular risk have been tested for potential benefit in ADRD treatment or prevention, with little success. The breadth of pathologies now recognized as relevant to ADRD provides many new pathways for therapeutic development, and novel biomarkers which may revolutionize the diagnostic process and provide opportunities to ensure target engagement. New interventions are needed for all stages of disease as well as for disease prevention.
Genetics of Pediatric-Onset Psychiatric Disorders
Authors: Levy Tess , Buxbaum Joseph D.
Published: January 2025

Pediatric-onset psychiatric disorders are substantially heritable, with various types of genomic changes contributing to risk. Extensive research, including genome-wide association studies, has shed light on the involvement of common genetic variation with modest effect sizes. In addition, sequencing studies have identified rare genetic variation within specific genes, which contributes to higher risk. The size of genetic changes associated with pediatric psychiatric disorders varies considerably, ranging from minute alterations involving a single base pair (most commonly as single nucleotide variation/polymorphism) to more substantial chromosomal changes such as aneuploidy or copy number changes. This chapter provides a comprehensive review of the genetics and heritability of several conditions, including autism spectrum disorder, attention-deficit/hyperactivity disorder, obsessive–compulsive disorder, and Tourette and chronic tic disorders. Significant advancements have been made in this field during the past decade, and the pace of this progress is projected to continue.
Neurobiology of Autism Spectrum Disorder and Intellectual Disability
Authors: Massa Alexandra , Costales Jesse , Rubeis Silvia De , Foss-Feig Jennifer , Hof Patrick R. , Kolevzon Alexander
Published: January 2025

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that first manifests in early childhood and is characterized by impairments in social communication and the presence of restricted and repetitive behaviors. Approximately one-third of affected children also experience intellectual disability (ID). The current understanding of the neurobiology of ASD and ID revolves around a few central findings, including synaptic dysfunction and imbalance between excitatory and inhibitory neurotransmission. This understanding relies heavily on genetic factors; studies have revealed that 500–1,000 genes may contribute to ASD risk. Many of the known ASD genes are also associated with ID without ASD. In addition to genetic studies, imaging and histopathological studies have contributed significantly to knowledge about the neurobiology of ASD and ID. This chapter integrates findings from human and animal studies using genetic, imaging, and histopathological methods to describe emerging themes in the understanding of ASD and ID.
Socialization and the Hidden Curriculum in Medical Professionalism
Authors: Lam Justin , Martimianakis M. A. , Hafferty F. W.
Published: January 2025

This chapter proposes a relational framework to explicate how the formal, informal, and hidden curricula socialize medical students to dueling professionalisms. Highlighted is how these curricula can often function as mechanisms for reproducing existing white, androcentric, and Eurocentric medical culture due to the way power circulates through medical education as a part of an enculturation process. Finally, the chapter demonstrates how the hidden curriculum—in the context of the framework—can be a powerful analytic tool for medical educators and researchers alike to anticipate and analyze curricular misalignments. By examining the implications for learner socialization through phenomena like learner mistreatment policies, evaluation of professionalism, and burnout, it is demonstrated how attention to hidden curriculum effects can connect individual experiences to issues at the level of structure and culture.
Professionalism of Solidarity and the Social Contract
Authors: de Carvalho Filho Marco Antonio , Franco Renato Soleiman , de Oliveira Vidal Edison Iglesias
Published: January 2025

The social contract metaphor brought to light the relationship between the medical profession and society with its reciprocity of duties and obligations. This enlightening allowed medical educators and professionals to debate the values of our profession while rescuing our social responsibility and accountability. It also allowed medical students to grip their learning trajectories toward becoming doctors. However, this metaphor may be insufficient to problematize an ever-evolving relationship in a dynamic, complex, and ever-evolving society by suggesting that our relationship with society is rigid with fixed rules and boundaries. This chapter expands this metaphor by bringing the critical pedagogy concepts of liberation, critical consciousness, full citizenship, education for change, and dialogue as connection and love and combine these concepts with cultural humility to suggest a professionalism of solidarity.
Professionalism and Conscientious Objection in Medicine
Authors: Wicclair Mark
Published: January 2025

This chapter examines conscientious objection from the perspective of medical professionals who have, or believe they have, a conscientious objection to a medical service; contemplate requesting an accommodation; and want to know whether conscientious objection is consistent with their professional obligations. The focus is on physicians and the medical profession. It provides answers to several important questions about conscientious objection in medicine. The following questions are addressed: (1) What does it mean for physicians to conscientiously object to a medical service? (2) What should members of the medical profession consider when deciding whether to conscientiously object and request an accommodation? (3) Should members of the medical profession be willing to inform and refer? (4) Should physicians be willing to explain their objections? (5) To whom, when, and how should members of the medical profession communicate their conscientious objections?
Spirituality and Professionalism
Authors: Merlo Gia
Published: January 2025

Being able to address a patient’s spiritual care needs and learning the tools for engaging in the provision of spiritual care can improve patient health outcomes and quality of life and help reduce the capacity for burnout while providing holistic, patient-centered care. Learning how to provide spiritual care to patients is—or should be—a domain of medical professionalism education. The high demands of spiritual care often pose difficulties for physicians during clinical interaction due to their perceived lack of competence and confidence in appropriately and effectively addressing the topic. This chapter discusses how and why spiritual care is an integral part of medical practice and medical professionalism education; different intervention models are provided to help physicians develop this aspect of their clinical practices.
Remediating Unprofessionalism Among Trainees
Authors: Wasserman Jason Adam , Redinger Michael J. , Gibb Tyler S
Published: January 2025

Professionalism is an essential trait for physicians, but it is a complex and multifaceted concept that is difficult to define and teach. There has been substantial focus on including professionalism in general curricula, but less emphasis on addressing and remedying instances of unprofessional behavior. Reframing professionalism lapses as analogous to medical errors and adopting a “just culture” approach both creates a safe learning environment and addresses problematic behaviors by trainees fairly and constructively. This approach views professionalism as a set of skills that require a supportive environment for development and recognizes that trainees may sometimes fall short as they learn to navigate ethical dilemmas and prioritize the needs of others over their own interests. This chapter articulates a just culture framework for addressing unprofessionalism and then describes methods and practices for addressing professionalism lapses.
Advocating for Diversity, Equity, Inclusion, and Social Justice
Authors: Smith Carlos S. , Razack Saleem , Reynolds P. Preston
Published: January 2025

Diversity, equity, inclusion, belonging, and justice (DEIBJ) are priorities in the education of health professionals today and will be into the future. Foundational aspects of DEIBJ education include skills in advocacy and community engagement and a deep understanding of historic injustices that continue to shape clinical encounters in all healthcare settings. Historically, every health profession denied admission to minority students and discriminated against minoritized patients well into the late twentieth century. Vestiges and impacts of those historic practices that continue as lived experiences of many patients today cannot be overstated. Fulfilling twenty-first century societal expectations of access to and care by competent health professionals who are skilled in communicating across ethnic and socioeconomic differences requires a reimagined professionalism with a focus on an anti-oppressive professionalism ethic as well as transformed learning environments, faculty, and curricula. Many events in the year 2020, such as a global outcry over racial injustices and a COVID-19 pandemic of unprecedented proportions, thrust a demand on academic health centers to provide a more inclusive learning experience and participation in a more equitable healthcare delivery system. This chapter addresses two priority areas: professionalism and the learning environment as primary actors in both professional identity formation and care delivery, as well as an anti-oppressive professionalism of inclusion as foundational to transformative learning.
Ibandronate Compared to Radiotherapy for Metastatic Bone Pain in Patients With Solid Tumors
Authors: Barlow Ashley , Bruera Eduardo
Published: January 2025

Bone pain related to metastatic solid tumors can contribute to significant morbidity and mortality. Beyond supportive care management with analgesics, radiation therapy has long been the standard of care to reduce the symptoms associated with metastatic bone pain. A single infusion of ibandronate, a bisphosphonate, was studied and found to have similar outcomes to radiation therapy, allowing for an expansion of treatment options in patients suffering from metastatic bone pain.
Methadone as a Coanalgesic
Authors: Bemben Nina M.
Published: January 2025

Inadequately controlled pain remains a challenge in patients receiving palliative care. This study sought to evaluate the efficacy of methadone as an adjunctive analgesic. It is a retrospective and prospective cohort study of patients treated with methadone as an adjunctive analgesic. Low-dose methadone improved analgesia by at least 30% in 49% of patients treated by a palliative care team when used as an adjunctive therapy. The median time to response was 7 days. Low-dose methadone is an effective add-on therapy for patients with inadequate analgesia on their current opioid regimen.
Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care
Authors: Davis Mellar P.
Published: January 2025

This randomized trial compared placebo, haloperidol, and risperidone in 247 patients with delirium. Delirium failed to improve with risperidone or haloperidol relative to placebo. Both antipsychotics had worse outcomes than placebo.
Haloperidol as an Adjunct Therapy for Pain and Nausea in Acute Gastroparesis
Authors: DiScala Sandra , Vartan Christine M.
Published: January 2025

This is a review and case application of a study by Roldan et al. titled “Randomized Controlled Double-Blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis.” Patients received either haloperidol 5 mg intravenously or placebo given in conjunction with conventional treatment. This trial demonstrated a significant trend of improved abdominal pain and nausea within 1 hour after haloperidol administration in adult patients with acute gastroparesis presenting to the emergency department. Secondary outcomes of hospitalization and length of stay also favored the haloperidol group. Haloperidol is used widely to treat nausea in the palliative care setting; therefore, this knowledge was used to apply a similar treatment strategy in the setting of acute gastroparesis.
Neuroleptic Strategies for Terminal Agitation in Patients With Cancer and Delirium at an Acute Palliative Care Unit
Authors: Jordan Allison E. , Gamble Alexander
Published: January 2025

This is a single-center, double-blind, parallel-group, randomized trial of patients with advanced cancer with refractory agitation who were treated for terminal delirium after not responding to low-dose haloperidol. Patients were randomized to dose escalation of intravenous haloperidol, neuroleptic rotation to chlorpromazine, or combined haloperidol and chlorpromazine. The primary outcome was a reduction in Richmond Agitation Sedation Scale (RASS) score in the first 24 hours. The RASS score decreased after 30 minutes of receiving the masked study medication and remained low for 24 hours for all 3 groups. The most serious adverse event was hypotension. No patients died from treatment.
Methylnaltrexone for Opioid-Induced Constipation
Authors: Higgins Elizabeth , Cain Joan , Blair Dwight
Published: January 2025

Opioid-induced constipation (OIC) is distressing for patients and may lead to inadequate pain control. Laxatives are often inadequate and burdensome for patients with OIC. Methylnaltrexone is a drug with selective antagonism of peripheral μ-opioid receptors (PAMORA) and does not affect the central nervous system. This study looked at patients with OIC and advanced illness and randomized them to receive either a placebo or methylnaltrexone at a dose of 0.15 mg/kg subcutaneously. The investigators were blinded. The study found that almost half of the methylnaltrexone group achieved laxation within 4 hours of the first study dose compared to only 15% in the placebo group. Methylnaltrexone appears to be a safe and effective drug that does not affect analgesia.
Donepezil and Memantine for Moderate-to-Severe Alzheimer Disease
Authors: Marchand Kristina , McGehrin Kevin
Published: January 2025

Palliative care clinicians encounter patients with late-stage Alzheimer disease who have been prescribed cholinesterase inhibitors and must decide whether to modify pharmacologic therapy. The Donepezil and Memantine in Moderate-to-Severe Alzheimer’s Disease (DOMINO) study evaluated patients already receiving donepezil after making adjustments to their therapy. Interventions included continuing donepezil alone, discontinuing donepezil, changing donepezil to memantine, or adding memantine to donepezil. Changes in cognitive and functional decline were measured 1 year after making adjustments to therapy. This study demonstrated a statistically significant difference in cognitive decline in patients continued on donepezil, but the clinical benefits were minimal.
Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting
Authors: Nguyen Cindy
Published: January 2025

Olanzapine is an effective second-generation atypical antipsychotic and antiemetic agent due to its antagonism at the dopamine, histamine, serotonin, and muscarinic receptors. Previous reports have revealed the effectiveness of olanzapine as an antiemetic agent for patients with advanced cancer, independent of chemotherapy. In this randomized, double-blinded, placebo-controlled trial, low-dose olanzapine 5 mg daily demonstrated statistical significance in reducing nausea and vomiting in patients with advanced cancer compared to placebo. After 7 days of treatment, the placebo arm’s median nausea scores were 9 out of 10 (range 8–10), compared to 1 out of 10 (range 0–3) in the olanzapine arm. Patients in the olanzapine arm experienced less sedation, less fatigue, and better well-being.
Ketamine
Authors: Wahlberg Lara , Singh Navendra
Published: January 2025

Ketamine is used to treat refractory cancer pain; there is poor evidence to suggest its continued use. A randomized, double-blinded, placebo-controlled trial assessed the efficacy of subcutaneous ketamine versus placebo in the setting of standard opioid and adjuvant therapy in the management of uncontrolled cancer pain over 3–5 days. There were no significant differences between the ketamine arm and the placebo arm in pain scores. There were more adverse events in the ketamine arm compared to the placebo arm. Ketamine does not have clinical benefit when used as an adjunct to standard therapy for cancer pain.
Imaging headache
Authors: Sulkin Tom , Mannava Amoolya , Kruger Ross
Published: January 2025

Over the past 50 years, radiological development has revolutionized investigation of headache. This chapter outlines the key principles of computed tomography and magnetic resonance imaging. Not everyone with a headache should be imaged. There will inevitably be a trade-off between clinical utility, cost, availability. The problem of incidental abnormalities should be discuss with the patient and imaging should be rarely undertaken for reassurance. A range of images and their diagnoses are added in the appendix.
Headache associated with CNS infection
Authors: Ahmed Fayyaz , Kernick David
Published: January 2025

This chapter covers the diagnosis and aetiology of meningitis and encephalitis. Post-viral and Covid headache are also considered.
Other problematic and rarer headaches
Authors: Kernick David , Ahmed Fayyaz
Published: January 2025

There are a wide range of miscellaneous headache types, many of which have not been fully validated. This chapter reviews some rare but important headaches that are not covered elsewhere.
Acupuncture for headache
Authors: Cummings Mike
Published: January 2025

Acupuncture studies have been difficult to interpret owing to lack of headache specificity and diagnostic rigour. Nevertheless, acupuncture has been recommended for migraine and tension-type headache by NICE. This chapter offers an overview of the use of acupuncture in headache, and describes a simple approach that can be effective.
Efficacy of Army Combat Fitness Test 12-Week Exercise Program Among Females
Authors: Heijnen Michel J H , Berni Angila , McNabb Phoebe , Caldwell Steven , Holland Stephen , Kawczynski Bill , McDaniel Alexander T , Noland Sarah , Strayhorn Shaila , Tseh Wayland
Published: January 2025

Introduction

The dearth of research investigating the efficacy of virtual Army Combat Fitness Test (ACFT) training programs among female populations necessitates further exploration. This study aims to evaluate the effectiveness of a 12-week ACFT virtual exercise program among female participants.

Materials and Methods

Nine female participants (age = 19.7 ± 1.3 years, height = 165.9 ± 4.9 cm, and body mass = 62.7 ± 5.9 kg) volunteered to complete 2 assessment sessions and the 12-week ACFT virtual exercise training program. In session 1, baseline height, body mass, body composition, and ACFT scores were collected. Upon completion of session 1, under supervisory guidance, all participants were scheduled to complete the 12-week exercise training program in-person. The ACFT exercise training program required participants to complete a warmup/cool down and exercise with suspension training straps 4 days per week, 60 minutes for 12 weeks. In session 2, post-assessments of body mass, body composition, and ACFT scores were collected. Statistical analyses were conducted utilizing paired sample t-tests to assess differences between pre- and post-intervention ACFT scores with P ≤ .05. Cohen’s d was calculated to quantify the magnitude of the observed effect.

Results

Overall mean ACFT pre-intervention scores (487.2 ± 66.5) increased significantly when compared to mean ACFT post-intervention scores (521.6 ± 44.0) (Cohen’s d = 0.86, P = .03). No statistical differences were displayed among the individual mean ACFT pre- versus post-intervention scores. A consistent decline in adherence of 3.9% per week ensued from week 1 through week 12.

Conclusions

Following the intervention, female participants experienced a significant increase of approximately 7% in their overall ACFT scores, with upward trends observed across all 6 individual ACFT events. These findings suggest that 12-week virtual suspension training can be a valuable tool for enhancing physical fitness and performance among female participants, particularly within the context of military readiness.
The gas-to-dust ratio investigation in the massive star-forming region M17
Authors: Zhao Qi , Jiang Zhibo , Wu Chao-Jian , Zheng Jie , Cheng Cheng , Zhu YiNan , Wu Hong
Published: January 2025

M17 is a well-known massive star-forming region, and its gas-to-dust ratio (GDR) may vary significantly compared to the other areas. The mass of gas can be traced by the ${\rm CO}$ emission observed in the Milky Way Imaging Scroll Painting project. The dust mass can be traced by analysing the interstellar extinction magnitude obtained from the United Kingdom Infrared Telescope. We computed the ratio ${W({\rm CO})/A_\mathit{ V}}$: for ${A_\mathit{ V} \le }$ 10 mag, ${{ W(^{12}{\rm CO})/ A_\mathit{ V}}= (6.27 \pm 0.19)}$${\mathrm{{K \, km\,s^{-1}}\, mag^{-1}}}$ and ${{ W(^{13}{\rm CO})/ A_\mathit{ V}} = (0.75 \pm 0.72)}$${ \mathrm{{K \, km\,s^{-1}} \, mag^{-1}}}$; whereas for ${{A_\mathit{ V}} \ge 10}$ mag, ${{ W(^{12}{\rm CO})/ A_\mathit{ V}} = (15.8 \pm 0.06) }$ ${\mathrm{{K \, km\,s^{-1}} \, mag^{-1}}}$, and ${{ W(^{13}{\rm CO})/ A_\mathit{ V}} = (3.11 \pm 0.25)}$ ${ \mathrm{{K \, km\,s^{-1}} \, mag^{-1}}}$. Then, we converted the ${W({\rm CO})/A_\mathit{ V}}$ into ${N(\rm H)/\mathit{ A}_\mathit{ V}}$. Using the WD01 model, we derived the GDR: for ${A_\mathit{ V} \le }$ 10 mag, the GDRs were ${118 \pm 9}$ for ${^{12}{\rm CO}}$ and ${83 \pm 62}$ for ${^{13}{\rm CO}}$, comparable to those of the Milky Way; however, for ${A_\mathit{ V} \ge }$ 10 mag, the GDRs increased significantly to ${296 \pm 3}$ for ${^{12}{\rm CO}}$ and ${387 \pm 40}$ for ${^{13}{\rm CO}}$, approximately three times higher than those of the Milky Way. In the discussion, we compared the results of this work with previous studies and provided a detailed discussion of the influence of massive stars and other factors on GDR.
Extracellular Vesicles Released by Glioblastoma Cancer Cells Drive Tumor Invasiveness via Connexin-43 Gap Junctions
Authors: Tamborini Matteo , Ribecco Valentino , Stanzani Elisabetta , Sironi Arianna , Tambalo Monica , Franzone Davide , Florio Elena , Fraviga Edoardo , Saulle Chiara , Gagliani Maria C , Pizzocri Marco , Mattioli Milena , Cortese Katia , Jiang Jean X , Martano Giuseppe , Politi Letterio S , Riva Marco , Pessina Federico , Pozzi Davide , Lodato Simona , Passoni Lorena , Matteoli Michela
Published: January 2025

Background

Although invasiveness is one of the major determinants of the poor glioblastoma (GBM) outcome, the mechanisms of GBM invasion are only partially understood. Among the intrinsic and environmental processes promoting cell-to-cell interaction processes, eventually driving GBM invasion, we focused on the pro-invasive role played by Extracellular Vesicles (EVs), a heterogeneous group of cell-released membranous structures containing various bioactive cargoes, which can be transferred from donor to recipient cells.

Methods

EVs isolated from patient-derived GBM cell lines and surgical aspirates were assessed for their pro-migratory competence by spheroid migration assays, calcium imaging, and PYK-2/FAK phosphorylation. Brain invasiveness was investigated in human cortical organoids-based assembloids and in vivo orthotopic xenografts. EV molecular features were specified by multiplex bead-based flow cytometry.

Results

Results unveil a self-sustaining mechanism triggering migration through autocrine release and engagement of a specific population of EVs of large size (L-EVs), isolated from either patient-derived cell lines or surgical aspirates. L-EVs act through modulation of calcium transients via Connexin 43-Gap Junctions (Cx43-GJ) and phospho-activation of PYK2. Pre-incubation with blocking antibodies targeting Cx43 hemichannels demonstrated a dose-dependent inhibition of the L-EV-mediated GBM migration. By exploiting patients’ surgical aspirates, we show that only L-EVs deriving from tumoral cells, and not those with immune origin, promote tumor migration, impacting more prominently the tumoral cells with mesenchymal subtype.

Conclusions

We demonstrate that L-EVs released by GBM cells, but not by the immune cells of the tumor microenvironment, represent a relevant and unique autocrine pro-migratory input for the tumor.
Race and ‘omic’ data in glioma: a systematic review of contemporary research to explore the digital divide
Authors: Dada Olaoluwa Ezekiel , Chisango Zvipo , Nkansah-Poku Kwadwo Antwi Boasiako , Sowah Mareshah N , Rodrigues Amanda Cyntia Lima Fonseca , Duru Olivia , Myers Matthew , Williams Sophie T , Ushewokunze Shungu , Collis Spencer J , Shlobin Nathan A , Omoruyi Sylvester , Rominiyi Ola
Published: January 2025

Background

The expanding repertoire of studies generating genome-scale omic datasets from glioma samples provides a generational opportunity to uncover mechanisms driving aggressive biology and develop new treatments. However, ensuring such studies reflect the breadth of racial groups and ethnicities affected by gliomas is critical to support equity in future therapeutic advances. We therefore report a contemporary snapshot of the representation of race and ethnicity in omic glioma studies.

Methods

We searched PubMed, Embase, Web of Science and Scopus and systematically reviewed articles published between January and November 2023 reporting de novo genome-scale sequencing data generated using samples from patients diagnosed with a glioma (according to WHO 2021 criteria) to characterise the reporting and composition of race and ethnicity data.

Results

Thirty-five studies involving 5,601 patients were analysed. Race or ethnicity data was reported in only 3 studies (8.6%), of which none provided omic data in a format that could be stratified by race or ethnicity. Reporting varied by continent with all 3 studies including race or ethnicity data based in North America. Where racial data was available, we found that samples used for genome-scale characterisation came from patients reported as being White in 91.1% cases (41 patients), with 6.7% (3 patients) reported as Black and 2.2% (1 patient) as Hispanic.

Conclusions

These studies underscore an urgent need for improved reporting and representation to enhance our understanding of glioma biology across different populations and guide targeted initiatives from policy makers and funders to support equitable improvements in healthcare.
Everything Everywhere All At Once: competition policy and industrial policy choices in an era of structural change
Authors: Coyle Diane
Published: January 2025

There is a clear revival of active industrial policy in many OECD economies. There is also a renewed activism in competition policy, with broad issues such as digital market power, the green transition, and geopolitics on the agenda of competition authorities. The new activism reflects technological transformations that are reshaping economic structures and hence presenting policy-makers with long-run supply-side economic challenges. In this context, there is no clear assignment of policy tools to different bodies, but rather a need for coordination of policies across domains. Nor can technical decision-making by economic regulators be separated from the need to make normative judgments about the strategic direction of the economy. This implies two fundamental unsolved institutional challenges: how to combine expert analysis with political legitimacy; and how to coordinate policies across bodies whose responsibilities or remits sometimes conflict.
Abuse of dominance: has the effects-based analysis gone too far?
Authors: Geradin Damien , Huijts Stijn
Published: January 2025

In 2008, following a long period of a so-called ‘formalistic’ approach to competition law, the European Commission adopted a more economic, effects-based, approach to the analysis of abuses of a dominant position. This included the use of an as-efficient competitor (AEC) test for price-based exclusionary conduct. However, more recently the EC warned about an overly rigid implementation of the effects-based approach. Moreover, in the period after 2008, the Commission and national authorities started to prioritize cases in digital markets, for which some of the concepts adopted in 2008 were less suitable. This ultimately led to the introduction of ex ante regulation of certain digital services in the Digital Markets Act. Against this background, the article seeks to answer whether the Commission did indeed pursue an effects-based analysis after 2008, whether this approach was responsible for the length of investigations and the Commission’s inability to deliver meaningful outcomes, whether ex ante regulation is a helpful response to these difficulties, and how the Commission should address the criticisms against the ineffectiveness of its enforcement of the prohibition against abuse of a dominant position.
Assessing coastal zooplankton in the St. Lawrence estuary: spatio-temporal patterns of taxonomic and functional biodiversity
Authors: Santo Mélanie , Calosi Piero , Winkler Gesche
Published: January 2025

Biodiversity assessment promotes information on the state of an ecosystem. Zooplankton, as a sentinel group at the basis of aquatic food webs, are, thus, an important component to monitor for ecosystem conservation and management. For the first time, we characterized biodiversity of coastal zooplankton along the shallow Northern shoreline of the lower St. Lawrence estuary (LSLE) using an integrated taxonomic and trait-based approach. For 3 years (2019–2021), in July and October, the zooplankton community and environmental parameters were sampled at < 35 m depth. Mesozooplankton were identified at the lowest possible taxonomic level and assigned functional traits. Community structure and diversities revealed high spatio-temporal variations among three different geographic sectors and between seasons, mainly driven by water temperature, Chlorophyll-a concentration and less by salinity. Hotspots of taxonomic and functional diversities occurred in different sectors in the same month, underlining the complementarity of the two approaches. Seasonal shifts in functional diversity hotspots highlight how environmental variability affects biodiversity beyond taxonomic metrics alone. The results of our study in the LSLE establish a first robust baseline to improve our understanding of zooplankton dynamics in the coastal LSLE, to allow future tracking of ongoing change due to the increase of anthropogenic activities and climate changes and to support future monitoring efforts.
Cultural fluency required? Interrogating ethnocentrism in the employment of white-collar Asian migrants in Japan
Authors: Holbrow Hilary J , Liang Hao
Published: January 2025

Scholars contend that Japanese firms hold white-collar foreign workers to a high bar for assimilation. This model of the ethnocentric firm suggests that Japan’s growing number of foreign-educated white-collar migrants should face steep labor market penalties compared to migrants educated in Japan because they have had fewer opportunities to familiarize themselves with Japanese working styles and norms. We test this hypothesis using a sample of 546 Asian white-collar foreign workers. However, we find that, robust to controls for compositional differences in the foreign- and Japan-educated migrant populations, foreign-educated migrants earn more. Since wage penalties for foreign degrees are ubiquitous in other national contexts, this finding counterintuitively implies that, at least in evaluation and rewards, Japanese firms may be less ethnocentric than the global norm.
Distinct seasonality of nutrients in twigs and leaves of temperate trees
Authors: Tian Yuehan , Du Enzai , Tang Yang , Xia Nan
Published: January 2025

Seasonal variations of nutrients in different organs are an essential strategy for temperate trees to maintain growth and function. The seasonal variations and variability (i.e., seasonality) of leaf nutrient concentrations have been well documented, while the trends and magnitudes of such seasonal variations in other tree organs (e.g., twigs) and their associations with leaf nutrients remain poorly understood. We measured the concentrations of ten nutrients (nitrogen, N; phosphorus, P; potassium, K; calcium, Ca; magnesium, Mg; iron, Fe; manganese, Mn; copper, Cu; zinc, Zn; boron, B) in twigs and leaves of four temperate tree species (i.e., Chinese pine, Ginkgo tree, Smoke tree, and Chinese scholar tree) to explore their seasonal variations and seasonality. Macronutrient concentrations (N, P, K, Ca, and Mg) were significantly higher in leaves while micronutrient concentrations (Fe, Mn, Cu, and Zn) were significantly higher in twigs. Concentrations of P and K both showed a negative seasonal covariation between twigs and leaves, while Ca, Fe, Mn, Cu, Zn, and B showed an opposite relationship. Compared with mobile nutrients, non-mobile nutrients exhibited significantly greater seasonality in the leaves but there were no such differences in twigs. The seasonality of nutrient concentrations in twigs was significantly stronger than in leaves. The seasonality of nutrient concentrations in twigs was positively correlated with that in leaves. Additionally, nutrients with higher physiological requirements in leaves showed weaker seasonality, confirming the hypothesis of seasonal stability of high-demand nutrients, while such relationships were not statistically significant for twigs. Our study demonstrates distinct seasonality of nutrients in twigs and leaves of temperate woody plants. These findings highlight that high-demand nutrients show stronger seasonal stability in leaves but not in twigs and uncover seasonal coordination between twigs and leaves as a nutrient conservation strategy.
Estimating Skeletal Maturity by Segmented Linear Modeling of Key AP Wrist Radiographic Parameters
Authors: Smith Kira L. , Furdock Ryan , Yuan Joshua T. , Chen Kallie J. , Liu Raymond
Published: January 2025

Background:

The recently described Modified Fels wrist skeletal maturity system (mFels wrist SMS) allows for accurate skeletal maturity estimation using a single anteroposterior wrist radiograph but requires evaluation of 8 parameters. A faster method may have clinical utility in the outpatient setting.

Methods:

The 8 anteroposterior wrist radiographic parameters comprising the mFels wrist SMS were analyzed in 80 children. Segmented linear regression and generalized estimating equation (GEE) analyses were used to identify the subsets of parameters most important for accurate skeletal maturity estimation for different patient demographics and parameter scores. This process produced multiple abbreviated Fels wrist skeletal maturity system options (abFels wrist SMS), which require fewer parameters. The accuracy of the resulting abFels wrist SMS options was evaluated and compared with the full 8-parameter mFels wrist SMS, the Greulich and Pyle system (GP) optimized with age and sex data, and the Sanders Hand System (SHS) optimized with age and sex data.

Results:

A total of 372 wrist radiographs from 42 girls (age range, 7 to 15 y) and 38 boys (age range, 9 to 16 y) were included. The abFels wrist SMS options required fewer parameters (range, 2 to 7 parameters, one option with 2 to 4 parameters) than the full mFels wrist SMS (8 parameters). Skeletal age estimates produced by the full mFels SMS were more accurate than GP (P<0.001), SHS (P<0.001), and similar to the all of the abFels wrist SMS options (P>0.05). The mFels wrist SMS made fewer outlier estimations (estimation >1 y off from the patient’s actual skeletal age) than GP (P<0.05), and made similar rates of outlier estimations compared with SHS (P>0.05) and the abFels wrist SMS options (P>0.05).

Conclusion:

An abbreviated version of the Modified Fels wrist SMS estimates skeletal maturity with comparable accuracy to the full version but only requires 2 to 4 parameters for quicker use.
Trend in the Use of Pain Modalities in Patients with Vascular Anomalies
Authors: Yi Avalon , Linn Jaimie , Ochmanek Emily , Fabre Anna , Yang MingAn , Smidt Aimee C.
Published: January 2025

Objective:

To investigate and describe methods of pain management employed by patients at a vascular anomalies clinic (VAC) with the intent to add relevant information on this important topic.

Methods:

Patients evaluated from 2011 to 2023 at the VAC at the University of New Mexico were invited to participate. Patients/guardians completed a REDCap survey recording demographics, self-identified diagnosis/type of vascular anomaly (VA), associated pain frequency/severity, pain management tried, and perceived effect(s). Diagnoses were verified/clarified by one of the authors (A.C.S.) when possible. Data was de-identified, analyzed, and reported using descriptive statistics.

Results:

In total, 95 patients were included; age range 1–81 years and mean age 22.14 years (sd = 18.43; w/Q1 = 9; Q2 = 16, Q3 = 33). Most common diagnoses were: venous malformation (n = 44) and lymphatic malformation (n = 22). Median pain rating (scale of 0–10) experienced daily was 1; 12% experienced pain daily; 5% 4–5 days a week, 13% 3–4 days a week, and 23% 1–2 days a week. Nonsteroidal anti-inflammatory drugs (32%) and acetaminophen (15%) were the most common over-the-counter medications reported. Nine percent reported using opioids; 9% reported use of cannabinoid-containing products. Of those who used opioids, 33% reported major pain relief pain. Of those who used cannabinoid-containing products, 50% reported major relief in pain.

Conclusions:

Pain is common in patients with VA; more than half of participants experienced pain at least weekly, regardless of VA type. Pain management methods varied, including over-the-counter remedies, cannabinoids, and opiates. Specifically addressing pain management in the VAC setting has the potential to positively impact quality of life and safety.
Evidence-Based Practice Attitudes of Neonatal Nurses
Authors: Taş Arslan Fatma , Küçükoğlu Sibel , Tar Bolacalı Edanur , Tanrıkulu Gözdenur , Ertürk Fatma
Published: January 2025

Objective:

This study aims to determine the internal and external factors affecting the attitudes of neonatal intensive care nurses toward evidence-based practices (EBP).

Methods:

The population of this descriptive, cross-sectional, and relation-seeking multicenter study consisted of nurses working in 5 neonatal intensive care units located in 3 provinces of Türkiye. Data were collected using the Information Form, which included nurses’ sociodemographic information and internal-external factors affecting evidence-based care practices, the Evidence-Based Nursing Attitude Questionnaire (EBNAQ).

Results:

It was found that sociodemographic characteristics of nurses impacted the EBNAQ score. Of the internal factors, knowledge of EBP, having a sufficient foreign language level to follow EBP, self-efficacy in the process of seeking, finding, evaluating, and applying evidence, belief in the necessity of using EBP in nursing care, belief that cultural differences affect EBP, and belief that EBP negatively affect individualized care affected the EBNAQ score. In terms of external factors, the competence of the study team in searching evidence, the employment institution supporting the team in the use of EBP, and using clinical guidelines in neonatal care impacted the EBNAQ score.

Conclusion:

It was concluded that neonatal nurses’ attitudes toward evidence-based nursing are at a moderate level and are affected by internal and external factors.
Risk factors that predict for presence of clinically significant, noncalcified plaque in younger adults
Authors: Mehta Aditya , Thomas Felix , Manubolu Venkat , Kinninger April , Budoff Matthew , Roy Sion K.
Published: January 2025

Objective

Coronary artery calcium (CAC) scoring may be a useful tool for assessing cardiovascular disease in young adults, particularly in those with risk factors such as hypertension, dyslipidemia, or smoking. In this study, we aimed to address the risk factors for developing noncalcified plaque in young adults by assessing total plaque burden.

Methods

A single-center retrospective cohort study was conducted among 1026 consecutive patients aged 18–45 years who underwent CAC scoring and coronary computed tomography (CT) angiograms for clinical indications. CAC scores and total plaque scores (TPS) were calculated using standard scoring protocols. Multiple logistic regression analysis was conducted to identify independent risk factors of significant, noncalcified plaque in subjects where CAC = 0.

Results

This single-center retrospective cohort study included 1026 patients aged 18–45 years who underwent CAC scoring and coronary CT angiograms for clinical indications. The mean age of the population was 38.8 years old. Sixty-three patients had a CAC score of 0 and a TPS >0. Of the patients with noncalcified plaque burden, 15% had a stenosis >50%, and 10% had a stenosis >70%. The odds of a subject having noncalcified plaque presence and CAC absent were significantly associated with being Hispanic, having diabetes, and having hyperlipidemia.

Conclusion

In young adults aged 18–45 years old, we found diabetes, hyperlipidemia, and being of Hispanic origin to be significantly associated with noncalcified plaque burden.