bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of interobserver and Intraobserver reliability of alpha angle measurements using different types of circles for femoroacetabular impingement syndrome
Authors: Aydin Özgür , Hapa Onur , Acar Emre , Celtik Mustafa , Agca Selahattin , Turemis Cihangir , Yarol Raif C , Aydemir Selahaddin
Published: January 2025

The alpha angle is a radiological measurement that has been proposed for the detection of cam morphology in patients suspected of femoroacetabular impingement syndrome (FAIS). After analysing published articles on FAIS, it is apparent that different types of circles are used in the measurement of alpha angles. To determine the interobserver and intraobserver reliability of alpha angle values measured using different types of circles on a 45° Dunn lateral radiograph in patients with symptomatic FAIS. The 45° Dunn lateral radiographs of the operated hips of patients who underwent hip preservation surgery in Dokuz Eylül University Hospital between 2014 and 2017 were evaluated retrospectively. Alpha angles were measured manually with transparent goniometers using three different circle types: thin full circle, thin-dashed circle, and thick full circle, and eye estimation without circle insertion. Measurements were made separately by an orthopaedist and a radiologist. A second measurement was made by the radiologist 1 month later for intraobserver reliability. Interobserver reliability for the thin full circle, thin-dashed circle, thick circle, and eye estimation (ICC = 0.645, 0.525, 0.494, and 0.588, respectively). Intraobserver reliability for the thin, thin-dashed, thick line, and eye estimation (ICC= 0.626, 0.681, 0.681, and 0.462 respectively). Interobserver difference of mean values of alpha angles for thin full, thin-dashed, thick full, and eye estimation were 2.7°, 0.9°, 1.1°, and 2.3°, respectively. Intraobserver differences between measurements were 1.5°, 0.9°, 0°, and 1.6°, respectively. Our study demonstrated that interobserver reliability is highest when measurements are made using a thin full circle.
Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1
Authors: Askari Kasra , Johnson Jennifer L , Shukla Aparna , Meneses-Salas Elsa , Kiosses William B , Yu Juan , Catz Sergio D
Published: January 2025

Regulated sequential exocytosis of neutrophil granules is essential in orchestrating the innate immune response, while uncontrolled secretion causes inflammation. We developed and characterized Nexinhib20, a small-molecule inhibitor that targets azurophilic granule exocytosis in neutrophils by blocking the interaction between the small GTPase Rab27a and its effector JFC1. Its therapeutic potential has been demonstrated in several pre-clinical models of inflammatory disease. Here, using neutrophils from Jfc1-KO mice, we show that JFC1 regulates the mobilization of a small subpopulation of CD11b+ granules. Nexinhib20 inhibits the mobilization of β2-integrins from a subset of CD11b+ granules to the plasma membrane in human and mouse neutrophils. The putative impact of Nexinhib20 on integrin activation is caused by decreased avidity, secondary to its effect on β2-integrin mobilization. CD11b mobilization and integrin activation were unaffected by pharmacological inhibition or activation of Rac1. Using quantitative 3-dimensional enhanced resolution microscopy, we show that neutrophil activation induces the recruitment of JFC1 to CD11b+ granules. Nexinhib20 decreased the localization of JFC1 at CD11b+ granules without affecting the association of Rac1 with CD11b. Nexinhib20 inhibits JFC1 recruitment but not endogenous Rac1 activation in living cells. Using orthogonal analyses of Rac1 activity consisting of a sensitive, time-resolved FRET, Rac1-PAK1-binding assay, and endogenous Rac1-GTP examination, we show that Nexinhib20 does not interfere with Rac1 activation. Instead, we confirmed its molecular mode of action to the inhibition of the Rab27a-JFC1 binding axis. Thus, Nexinhib20 limits β2- integrin mobilization to the cell surface, decreasing avidity, affecting active integrin availability, in a JFC1-dependent but Rac1-independent manner.
Hang in there: Capacity constraints and processes of sustaining collaboration over time
Authors: Seo Danbi
Published: January 2025

Sustaining collaboration over time is vital for its effectiveness and long-term success but presents challenges, especially for actors with capacity constraints. This study introduces “capacity tensions” as a central challenge in collaborative efforts, referring to the strain that arises when the capacity needed for effective engagement exceeds the capacity actors have available. This gap creates competing demands, as actors must balance what they can realistically contribute with what the collaboration needs to remain viable and successful. Focusing on a nonprofit collaboration that, despite ongoing capacity constraints, persisted with notable achievements, this study investigates how actors navigate and manage these tensions to sustain their efforts. By analyzing 165 interviews conducted over 11 rounds, participant observations, and archival documents from 2016 to 2020, this study identifies strategies of internal accommodation and external orientation. These strategies enabled actors to “hang in there” by assembling different contributions; tailoring work process; searching for relevant opportunities; and creating spin-off projects. Examining these strategies across three phases of collaboration over five years, this study proposes a process model that offers insights into sustaining effective collaboration despite capacity tensions. These findings provide valuable guidance for practitioners and scholars striving to build sustainable and resilient collaborations.
Papillary thyroid carcinoma within struma ovarii: a case report and literature review
Authors: Qaradakhy Aras J , Ali Rawa M , Ali Rebaz M , Yasseen Hadeel A , Hussein Shvan M , Abdullah Hiwa O , Hassan Shko H , Ahmed Harun Amanj , Salih Abdulwahid M , Othman Snur , Kakamad Fahmi H
Published: January 2025

Struma ovarii (SO) is a rare ovarian teratoma mostly made of thyroid tissue, with papillary thyroid carcinoma (PTC) being even rarer. This report presents a 50-year-old woman with PTC in SO and a normal thyroid. A left ovarian cyst was detected by ultrasound and confirmed by MRI. Surgery included total abdominal hysterectomy with bilateral salpingo-oophorectomy, revealing focal PTC and no thyroid abnormalities. A review of 10 cases showed a median diagnosis age of 46.5 years, with symptoms like abdominal pain and vaginal bleeding. Routine checkups in perimenopausal women are key for early detection, and thyroid evaluation is important in PTC cases within SO.
Happy birthday dear BNOC, happy birthday to you
Authors: Roberts Peter
Published: January 2025

This year marks what would have been the 50th birthday of the British National Oil Corporation (BNOC), which came into existence through the enactment of the Petroleum and Submarine Pipelines Act 1975. This article considers why BNOC came into being, why BNOC ceased to function after a relatively short period of time, and whether any lessons could be learned from BNOC’s past that could be helpful in shaping future energy regulatory policies.
Session 6: Working with Your Thoughts (Part I)—Coping Self-Statements
Authors: Beck J. Gayle
Published: January 2025

This chapter introduces skills that will help clients to work with negative thoughts, particularly developing and using coping self-statements. Cognitive therapy techniques are designed to address common elements of thinking, such as negative self-talk and distortions in perception, and can help clients to become aware of the underlying assumptions that guide their thinking. Coping self-statements can be useful when clients are facing stressful or challenging situations. Clients can learn to use coping self-statements to challenge the stream of negative self-talk that is common among individuals with PTSD. If time permits, this session can also include practice with progressive muscle relaxation.
Group Cognitive Behavioral Therapy for PTSD
Authors: Beck J. Gayle
Published: January 2025

Group Cognitive Behavioral Therapy (CBT) for PTSD : Client Workbook for Veterans assists clients who are participating in a Group Cognitive Behavior Therapy and is designed to be used with the accompanying Therapist Guide. The Client Workbook provides a concise overview of each chapter, along with information sheets and worksheets to facilitate between session practice. This treatment program integrates best practices derived from group therapy with evidence-based cognitive behavioral approaches to target PTSD and frequently co-occurring conditions ( depression, anger, and social isolation). Tested with both Veteran and non-Veteran populations, Group CBT has been proven to reduce symptoms of PTSD and improve quality of life, overall functioning, and life satisfaction. Essentially, the Client Workbook is designed to track progress and facilitate mastery of specific CBT techniques, to enhance mental well-being.
Session 11: Feeling Down— How to Fight It
Authors: Beck J. Gayle
Published: January 2025

This chapter focuses on how to address feelings of depression and low mood. Depression can become a problem when these feelings become more pronounced or when they last for several weeks. Depression can interfere with people's enjoyment of lifeand acknowledging depression can help begin the fight on days when the mood is really low. This session introduces pleasant activity scheduling, which helps to remedy the imbalance between negative and positive interactions with the world around you. The goal is to increase both the quantity and quality of positive interactions, with the result being an improved mood. A worksheet is included to help clients determine their beginning level of positive interactions to guide pleasant activity scheduling.
Development of the Hippocampal Formation
Authors: Lavenex Pierre , Amaral David G. , Banta Lavenex Pamela , Guillemot François , Insausti Ricardo , Urban Noelia
Published: January 2025

This chapter describes the developmental periods and processes that contribute to the structural maturation of hippocampal circuits. It establishes a comparative timeline describing specific developmental processes occurring in mice, rats, monkeys, and humans in order to summarize the general principles of the development of the hippocampal formation that are valid across species, and to point out important species differences. It considers specific genes and regulatory pathways controlling the early patterning of the hippocampal primordium, the migration of progenitor cells and neurons, and the establishment of connections of hippocampal neurons leading to the formation of functioning circuits. Finally, it discusses recent studies on the postnatal development of the hippocampal formation, ranging from structural MRI studies in humans, to structural and molecular studies in nonhuman primates, to functional studies in rodents, which collectively provide a coherent framework to understand the emergence of hippocampus-dependent memory during early childhood.
Synaptic Function
Authors: Kullmann Dimitri M. , Volynski Kirill E.
Published: January 2025

This chapter examines the fundamental operation of synaptic transmission. It describes how individual synapses in the hippocampus are specialized to transmit and process signals and encode a history of their recent activity. It provides an overview of the mechanisms of presynaptic release of neurotransmitters, outlines the diversity of glutamatergic GABAergic synapses, considers other neurotransmitters and receptor systems, and highlights some of the unresolved issues surrounding synaptic function.
Mesial Temporal Lobe Epilepsy
Authors: Walker Matthew C. , Thom Maria , Vivekananda Umesh
Published: January 2025

Seizures commonly arise from the mesial temporal lobe, and “scarring” of the hippocampus, hippocampal sclerosis, is the commonest cause of drug-resistant epilepsy. Hippocampal sclerosis stems from genetic and environmental factors, including traumatic brain injury, prolonged seizures, or inflammation. The hippocampus is not only the origin of seizures but also susceptible to damage from them, which can result in disease progression. Epilepsy, the occurrence of spontaneous seizures, results from structural and functional changes in hippocampal networks. A host of different processes, including inflammation, neuronal death, and changes in gene expression, drive the network changes that eventually result in epilepsy. Targeting these processes may prevent epilepsy or its progression. While many of these changes may be compensatory in reducing seizure frequency, they can impact cognition and mental health. Indeed, there is growing evidence that the pathophysiology of epilepsy-related hippocampal sclerosis overlaps with other conditions such as Alzheimer’s and neuropsychiatric disease.
Seeing Depression Through A Cultural Lens
Authors: Fogel Barry S. , Jiang Xiaoling
Published: January 2025

Seeing Depression through a Cultural Lens, the collaborative work of a clinical neuroscientist and a scholar of comparative culture, examines the effects of cultural identity on the epidemiology, phenomenology, and narratives of depression, the bipolar spectrum, and suicide. Culture is associated with emotional communication style, “idioms of distress,” the conception of depression and of bipolar disorders, and how people with mood disorders might be stigmatized. It is linked to structural factors—environmental, social, and economic circumstances—that create or mitigate the risk of depression, sometimes precipitate episodes of illness, and facilitate or impede treatment. Culture shapes depressed people’s willingness to disclose or acknowledge their condition and to seek care, their relationships with clinicians, and their acceptance or rejection of specific treatments. Cultural context is essential to understanding suicide. It underlies people’s motives for suicide, facilitating and inhibiting factors, the social acceptability of death by suicide, and the availability of lethal means of self-harm. Cultural identity is always intersectional—comprising elements related to race and ethnicity; gender; age, generation, and life stage; education; social class; occupation; migrant or minority status; region of residence; and religious belief and practice. Seeing Depression through a Cultural Lens explores the implications of each of these dimensions using salient concepts form the social sciences; memorable narratives from literature, film, and the clinic; and quantitative findings from epidemiology and psychometrics. It offers readers a framework for culturally aware assessment and management of depression, bipolarity, and suicidal risk in individuals and in populations.
Preoperative Process
Authors: Keshock Maureen , Cummings Kenneth
Published: January 2025

Significant changes have occurred in the design and setup of preoperative evaluation clinics as more patients plan elective surgery. These clinics improve rates of surgical delays, complications, hospital length of stay, cost, and day-of-surgery cancellations. The preoperative clinic is associated with the institution’s surgical site (hospital or ambulatory surgical center) and depends on the organization’s culture, goals, and existing resources. In all cases, the preoperative process ensures chart compilation, risk stratification, and compliance with regulatory bodies, although not all patients undergo the same process, varying based on surgical case risk and patient risk. The authors review various pre-anesthesia clinic models and the preoperative screening process. Technological advances and telemedicine in the form of virtual visits are explored, along with a screening algorithm embedded in the electronic medical record.
Cardiopulmonary Exercise Testing
Authors: Dove Paris , Traer Emily , Ismail Hilmy , Riedel Bernhard
Published: January 2025

Perioperative cardiopulmonary exercise testing (CPET) is a validated objective method of providing individualized and stratified preoperative risk assessments. Using gas-exchange analysis during a symptom-limited exercise ramp protocol, typically conducted on a cycle ergometer, dynamic oxygen utility and pulmonary carbon dioxide transport are measured. While functional capacity is not accurately predicted at rest, CPET offers an objective dynamic assessment of exercise tolerance, cardiopulmonary health, and specific cardiopulmonary limitations. Each test is a point of care, where perioperative education is provided and potential perioperative complications are elucidated. Complications may then be mitigated through patient-specific prehabilitation, optimization of modifiable risk factors, improved multidisciplinary communication, and planned postoperative care.
Does Your Cataract Surgeon Know You Were Admitted for Heart Failure Last Week?
Authors: Curtis Michael , Weitzel Nathaen , Kertai Miklos D.
Published: January 2025

Heart failure is a broad diagnosis encompassing a wide variety of etiologies, all generally manifesting as an inability for either the heart to meet the output required by the rest of the body or an inability to handle the systemic venous return. Given the significant stress placed on the cardiovascular system by anesthetics and surgery, patients with heart failure (who already have a borderline cardiac function) are at increased risk of perioperative adverse events, especially if not medically optimized. The preoperative evaluation can play a significant role in both devising a safe anesthetic plan for a patient and determining appropriate timing for procedures with respect to a patient’s current function.
Difficult Conversations
Authors: Ostapenko Laura J. , Hill Katherine A.
Published: January 2025

Healthcare clinicians have difficult conversations daily. In fact, these conversations are so ubiquitous that clinicians often do not realize the cognitive and emotional stress that these conversations cause—for patients, other care providers, and even the clinicians themselves. Research-validated tools exist to help clinicians have difficult conversations with less stress. Certain specialties within medicine, such as oncology and palliative care, have developed strategies for success in difficult conversations, where success is defined as a partnership between participants who work together to construct a shared medical context that is then used to make decisions about medical care based on a patient’s goals and values. Such strategies for having a successful difficult conversation share an underlying framework including agreeing on the medical context, responding to emotion, clarifying values in the setting of that medical context, and making a recommendation.
This Patient Has 17 Allergies: Including “General Anesthesia”
Authors: Pulley Debra D.
Published: January 2025

Medical care exposes patients to numerous chemical compounds that have the potential to cause hypersensitivity reactions. This is especially true at the time of surgery, when it may be difficult to discern what caused the reaction since there can be multiple simultaneous exposures. Many times, clinicians will simply avoid the causative agent; however, this is not always possible because alternative drugs may be inferior or simply not available. Accurate documentation of the reaction is vital. Relying on patient-provided information may not be reliable. Referral to an allergist can be useful. Thyroid disease is prevalent. Symptoms/signs suggestive of either hyperthyroidism or hypothyroidism should be assessed and elective surgery postponed if optimization is needed. Patients with goiter need preoperative airway assessment to identify potential airway compression.
Somatization in children and adolescents across cultures
Authors: Velusamy Arul , Sravanti Lakshmi
Published: January 2025

Somatization is ‘a tendency to experience and communicate somatic distress and symptoms unaccounted for by pathological findings, to attribute them to physical illness, and to seek medical help for them’. Somatization in children, as in adults, describes the presence of a range of physical symptoms not accounted for by physical pathology, which have an emotional or a communicative function, but could be attributed by the child, family, or both to an undiagnosed physical illness. Cultural factors play a significant role in somatization, influencing symptom expression, health-seeking patterns, and family and societal beliefs. This chapter conceptualizes somatization in children and adolescents through the lens of developmental psychopathology incorporating biopsychosocial and ecological systems frameworks, and discusses the impact of culture on somatization in children and adolescents and culture-bound syndromes in adolescents.
Somatization disorders in central and western Asia
Authors: Anuk Dilek
Published: January 2025

Somatization is one of the psychiatric disorders that is the most influenced by culture, occurring more commonly in more traditional societies in central and western Asia than in Europe. To understand the reasons behind such high somatization prevalence rate in this part of the world, factors such as the meaning of disease symptoms, upbringing styles, gender roles, divorce, stigma associated with psychiatric disorders, symbolic language, trauma, and migration that affect somatization in the culture in which patients are raised need to be taken into consideration. It is likely that the physical complaints in somatization have a communicative function peculiar to particular societies that goes beyond the standard meanings attributable to body language. They may also be a silent cry for help, a reflection of traumas, a sign of a need for support, and sometimes an expression of difficulty in adapting to a new environment.
Somatization disorders in South America
Authors: Ramalho Rodrigo , Berrio Cuartas Diana M. , Libuy Javiera , Parodi Claudia , Argomedo-Ramos Gianfranco , Vicente Spadini Alex , Gonzalez-Diaz Jairo M.
Published: January 2025

Somatization disorders in South America explores the influence of culture on somatization. Focusing on Latin America and the Latin American diaspora, the chapter examines how culture impacts the experience of somatization, its associated help-seeking behaviors, and the ways in which this help is received, while paying attention to how culture equally shapes psychiatric nosology and mental health-related clinical and research practices. It also critically reviews the literature, exploring the prevalence of somatization in this population. The chapter also discusses somatization, anxiety, and depression in primary care, as well as susto and nervios, two cultural concepts or idioms of distress. It also offers recommendations for clinical assessment, healthcare support, and research, emphasizing the importance of cultural safety and promoting diversity, inclusion, and health equity outcomes.
Understanding the reasons for self-harm
Authors: Quarshie Emmanuel Nii-Boye , House Allan
Published: January 2025

In this chapter we start with a review of the risk factors for self-harm, which can be summarized as: membership in a vulnerable group; problematic current circumstances; individual characteristics and recent stressful experiences. We discuss the individual reasons for which people self-harm—as a way of responding to or managing unpleasant emotions, communicating with others, or generating positive feelings. Putting information about these factors together into a formulation allows for a fuller understanding of the reasons for an episode of self-harm. Many of the same considerations are important in estimating the likelihood of repetition of self-harm or of subsequent suicide.
Neurology
Authors: Raine Tim , Collins George , Brown Fraser , Howarth Sophie
Published: January 2025

This chapter discusses the diagnosis and treatment of neurological conditions. It covers emergency treatment of coma and reduced GCS, adult seizures, paediatric seizures, and stroke/CVA/TIA. The chapter also includes discussion of focal neurology, functional neurological disorder, seizures, neurodegenerative disorders, stroke, back pain, headache, and dizziness.
Considering and responding to risk when working with people living with mental health problems
Authors: Warrender Dan , Young Chris
Published: January 2025

Risk is one of the most complex and anxiety-provoking issues faced by mental health nurses, with huge potential for not only helping but also significantly harming service users. Often considered narrowly in terms of violence and suicide, risk is best thought of more broadly as the potential of losing something of value. ‘How-to’ guides to risk may be fruitless when human beings are so complex, thus this chapter defines risk, identifies core foundational principles and relational practice required when working with service users, and presents models and discussion to aid critical thinking and reflection. The action/consequences model offers a thinking aid for decision making, considering how containing risk and tolerating risk can have a variety of outcomes, each of which can help or harm.
Skills to improve care continuity: Working in interagency and interprofessional teams
Authors: Weaver Nick , Hannigan Ben
Published: January 2025

Care for people with mental health difficulties is provided by practitioners often working in different teams and organizations. This makes the system of mental health a complex one and places a premium on continuity of care. Care continuity is a cornerstone of modern mental healthcare and one of the principal aims of care coordination. Mental health nurses have important parts to play in these areas. This chapter explores interprofessional and interagency working and introduces evidence and skills useful to nurses in their roles as care coordinators. Key skills must be developed and applied in working across multiple service interfaces with the aim of promoting care continuity. These include facilitating better continuity and connectivity across service boundaries, developing better therapeutic relationships, providing greater flexibility for service users, and supporting better communication and information transfer. The policy context is also important for developing interagency and interprofessional skills to promote better care continuity.
How Do I Manage My Adult Patient in the Hospital in a Vaso-occlusive Crisis?
Authors: Smith Wally R.
Published: January 2025

This chapter recommends pain management for hospitalized patients with a sickle cell disease (SCD) vaso-occlusive crisis (VOC). This chapter explains that hospitalization for a VOC is actually rare, compared to the number of days patients with SCD spend in pain. It recommends guideline-backed pain management practices, along with specific management tips that will likely shorten the time to discharge and eliminate unnecessary pain and suffering. It notes routes of administration with techniques for handling administration of parenteral opioids. It discusses repeated pain assessment with strengths and weaknesses of pain measures. The chapter recommends assessment variables for determining appropriateness of discharge.
How Do I Respond When My Patient Comes to the Clinic Asking for More Opioids Than Usual?
Authors: Carroll C. Patrick
Published: January 2025

This chapter guides clinicians through a set of simple questions they may use in their clinical strategy for managing seemingly worsened outpatient sickle cell disease (SCD) pain, whether or not it is called a vaso-occlusive crisis (VOC) by the patient. The pain experience of people with SCD varies over time. Often, pain evolves from episodic VOCs in early life to chronic pain with superimposed VOCs later. Complications that are independently painful can also accumulate. Thus, deciding when and whether to apply an acute pain treatment paradigm versus a chronic pain treatment paradigm can be difficult. Treatment is even more fraught with difficulty by the neuropharmacological complexity and risks of opioids. This chapter suggests how to deliberately choose a specific treatment paradigm based on answers to the above simple questions; how to assess whether that paradigm worked, including when to declare failure of opioids; and how to manage treatment and other risks in this subset of patients.
Optogenetics and Related Technologies for Psychiatric Disease Research
Authors: Fenno Lief E. , Deisseroth Karl
Published: January 2025

Causal study of brain function in model organisms is a central goal of neuroscience, and this work is critical to opening new frontiers in the management of psychiatric disease. Optogenetics—the use of light-activated proteins to directly control the activity of defined populations of neurons in awake, behaving animals—has revolutionized neuroscience and is being investigated for clinical use for the direct treatment of human neurological disease. This chapter serves as an introduction to the development of optogenetics, describes the use of this tool class in modern systems neuroscience and applications to understanding mental illness, and outlines current efforts to further develop this technology. Readers can expect to gain a sufficient mechanistic understanding of optogenetics to understand current primary neuroscience research, become familiar with this class of molecular techniques, and to be able to use the text as a reference for further reading.
Genetics of Schizophrenia
Authors: Legge Sophie E. , Pardiñas Antonio F. , O’Donovan Michael C.
Published: January 2025

Schizophrenia is a highly heritable, multifactorial disorder, the genetic component of which involves thousands of risk alleles. Risk loci identified include approximately 287 single nucleotide polymorphisms of very small effect with allele frequencies greater than 5%, up to 11 copy number variants of large effect with frequencies lower than 0.1%, and 10 genes containing ultra-rare damaging coding variants of large effect with frequencies of 0.01% or less. No known single allele accounts for an appreciable amount of population variance in risk or is alone sufficient to cause the disorder. Schizophrenia risk alleles are often pleiotropic, affecting cognitive traits and other psychiatric and neurodevelopmental disorders. Convergent evidence from risk alleles of all types suggests that central nervous system neurons are the most important site of pathophysiology. There is particularly strong evidence pointing to synaptic processes involving glutamatergic and GABAergic transmission, but other aspects of neuronal function are almost certainly involved.
Molecular and Cellular Mechanisms of Bipolar Disorder
Authors: McClung Colleen A. , Blumberg Hilary P.
Published: January 2025

This chapter describes findings from cell culture, animal, and human studies that have shed light on the molecular and cellular basis of bipolar disorder. It summarizes the most replicated genetic findings and the contribution of environmental influences. It also details the various cellular and brain circuit abnormalities that are thought to play a role in the development of this disorder. Sleep–wake and other circadian rhythm disruptions are central to the disorder; thus, a good portion of the chapter details how disruptions to normal 24-hr rhythms in a variety of cellular processes could contribute to bipolar disorder pathophysiology and treatment. In addition, the chapter discusses ways in which mood-stabilizing medications are thought to work therapeutically and how this has enhanced knowledge of the causes of this disease and how it may vary from individual to individual.
Neuroimaging and Circuit Mechanisms of Depression
Authors: Romer Adrienne L. , Bertocci Michele A. , Phillips Mary L. , Pizzagalli Diego A.
Published: January 2025

Major depressive disorder (MDD) is the leading cause of mental and behavioral disorder disability in the United States. MDD is characterized by dysfunctions in three primary processes: (a) emotion processing and regulation, (b) reward processing and learning, and (c) executive functioning (cognitive control). Neuroimaging research has identified neural alterations in MDD in frontolimbic, frontostriatal, and frontocingulate neural circuitries that support these three processes. This chapter details the neural circuit mechanisms underlying depression by reporting findings from studies using a variety of neuroimaging techniques, including functional and structural magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, arterial spin labeling, and magnetic resonance spectroscopy. The chapter concludes with discussions of promising new areas of neuroimaging research in depression, and it outlines important future directions for identification of robust biomarkers of depression that can increase diagnostic precision and guide personalized treatments.
Animal Models of Mood Disorders
Authors: Parise Lyonna F. , Cardona-Acosta Astrid M. , Parise Eric M. , Bolaños-Guzmán Carlos A.
Published: January 2025

Animal models have a crucial practical value for aiding the mechanistic understanding underlying mood disorders. Studying the central and peripheral mechanisms that mediate both normal and abnormal behavior has greatly advanced the development of pharmacological therapies to treat major depressive disorder. Ideally, a behavioral model should recapitulate the symptoms of the disorder that is observed in humans and should be sensitive to pharmacological interventions. Whether to evaluate stress-induced changes during a particular stage of development or to determine sex differences, there is an ideal animal model that can parallel the alterations seen in the human condition and therefore be ideal for evaluating therapeutic interventions or monitoring long-term outcomes. As knowledge advances, there will be increased utility for traditional testing protocols while also taking advantage of more sophisticated techniques to enhance old paradigms and ensure that the complexity with which animal models are employed is relevant and beneficial to real-world applications.
Novel Approaches for Treating Depression
Authors: Nestler Eric J. , Charney Dennis S. , Krystal John H. , Murrough James W.
Published: January 2025

Despite an improved understanding of mood regulation and the pathophysiology of depression, it has been extraordinarily difficult to generate antidepressant medications with truly novel mechanisms of action. A major milestone in the field was the approval of the first two non-monoamine-based antidepressants in the United States in 2019. Ketamine (which is an NMDA glutamate receptor antagonist among other actions) was approved for treatment-resistant symptoms of depression and depression in the context of increased suicide risk. Brexanolone (a positive allosteric modulator of the GABAA receptor) was approved for the treatment of postpartum depression. The expectation is that these approvals are a harbinger of many additional advances in antidepressant treatments that will be seen in the years ahead. This chapter summarizes the obstacles that have hindered the development of non-monoamine-based antidepressants, and it provides a progress report on some of the most promising current strategies.
Novel Approaches for Treating Anxiety and Trauma-Related Disorders
Authors: Kaye Alfred P. , Jefferson Sarah , Krystal John H.
Published: January 2025

Anxiety spectrum disorders are characterized by a pathological perception or response to threat. Treatments for anxiety frequently rely on utilizing neural plasticity to reduce threat response via extinction learning. Current treatments for anxiety involve sustained reduction in anxiety via antidepressants, anxiolytics, and psychotherapy. Although these treatments are effective, there is a large treatment-resistant population and a larger population that does not receive these treatments. Opportunities to reduce the burden of anxiety may target novel neural circuit or receptor targets that are not directly approached with current treatments. Both ketamine and psychedelic drugs may act in part by enhancing neural plasticity related to fear extinction. Direct modulation of neural circuits, using implanted devices of noninvasive means, may offer innovative and precise treatments. Finally, the utilization of computational approaches to behavior including virtual reality may enable scalable means of improving anxiety.
Current Treatments for Substance Use Disorders
Authors: D’Sa Adam , Gaddis Andrew L. , Strain Eric C.
Published: January 2025

This chapter reviews current pharmacological treatments of substance use disorders. The focus is on pharmacotherapies that are currently approved by the U.S. Food and Drug Administration (FDA), categorized by the appropriate substance use disorder. The evidence for approved pharmacotherapies for opioid use (methadone, buprenorphine, and naltrexone) and withdrawal (lofexidine) is discussed first. Then, the three first-line therapies for nicotine use disorder are evaluated: nicotine replacement, buproprion hydrochloride, and varenicline tartate. Next, the chapter discusses the three pharmacological treatments for alcohol use disorder: disulfiram, naltrexone, and acamprosate. No FDA-approved pharmacotherapies currently exist for cocaine, amphetamine, benzodiazepine, or cannabis use disorder. The chapter concludes with a discussion of future directions of drug development for substance use disorders.
Molecular and Cellular Mechanisms of Alzheimer’s Disease
Authors: Howell Gareth R. , Carter Gregory W.
Published: January 2025

Late-onset Alzheimer’s disease (LOAD) is a heterogeneous disorder with a complex genetic and environmental etiology. Animal models are the primary means to understand the mechanisms that drive the origin and progression of disease. Limitations of prior models have motivated new approaches to animal and cell modeling. The proliferation of molecular characterizations of Alzheimer’s disease through imaging, biomarkers, genetic, and multi-omic studies of clinical cohorts is enabling precision modeling in vivo and in vitro. This chapter describes how genetic editing is being used to create mouse models based on contemporary human genetics and how these new models are characterized using multiple modalities to optimally align with human studies. This approach to decipher the complexity of human LOAD using iterative modeling in mouse and other systems promises to facilitate the development and preclinical testing of precision molecular therapeutics for Alzheimer’s disease.
Neurobiology of Attention-Deficit/Hyperactivity Disorder
Authors: Levy Tess , Buxbaum Joseph D.
Published: January 2025

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent, early onset, and persistent disorder of inattention, hyperactivity, and impulsivity. ADHD has been associated with a range of adverse functional outcomes during childhood (e.g., school and social problems), adolescence (e.g., early onset and elevated substance use), and adulthood (e.g., reduced income and life span). Dysregulation of the catecholaminergic neurotransmission in cerebellar–corticostriatal circuits has been implicated in ADHD through successful pharmacological treatment, neuroimaging studies, and animal models. Medications have been largely successful in treating the core symptoms of ADHD. Hypotheses about the etiology of ADHD encompass genetic and environmental risk factors. Both common and rare genetic variants have been implicated in ADHD. Environmental factors, especially those that impact early neurodevelopment, have also been linked to ADHD risk.
Neurobiology of Eating Disorders
Authors: Hildebrandt Thomas , Susanin Annabel
Published: January 2025

This chapter provides a summary of the primary neurobiological understanding of eating disorders using experiments from animal models and the growing literature in humans. It discusses how dysregulation in appetite hormones and peptides, adrenal hormones, and ovarian hormones all show strong correlation to the development and maintenance of eating disorders. The chapter also addresses the role of the serotonergic and dopaminergic systems and several central nervous system neurocircuits in these chronic and frequently relapsing disorders. It highlights the developmental models, neural substrates, temperament and eating behaviors, and animal models used to understand anorexia nervosa, bulimia nervosa, and binge eating disorder. It also identifies future directions of neurobiological research in this field.
The Present and Future of Psychiatric Diagnosis
Authors: Hyman Steven E.
Published: January 2025

The 5th edition, text revision, of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the similar International Statistical Classification of Diseases and Related Health Problems, 11th edition, are the most widely used diagnostic systems for mental disorders. The DSM system makes diagnoses based on explicitly specified (operationalized) diagnostic criteria ascertained from the history of illness and clinical observation. The DSM system conceptualizes disorders as discrete categories discontinuous from health and completely distinct from each other. However, information from clinical research, genetics, molecular analyses of postmortem brains, epidemiology, and data sciences indicates that the categorical approach of the DSM is fundamentally in error and that mental disorders are better understood as quantitative deviations from health that overlap each other. Across disorders, there is significant sharing of genetic risk (shared risk alleles) and clinical overlap that the DSM interprets as comorbidity involving multiple distinct disorders.
Digital Assessments of Psychiatric Disorders
Authors: Quist Rachel E. , Bhattacharya Sukanya , Chacko Sarah M. , Jacobson Nicholas C.
Published: January 2025

There is a well-documented gap between the need for mental health treatment and the availability of these resources. Ecologically valid data collection is becoming increasingly more feasible through the increased everyday use of smartphones, wearable devices, and social media. These modes of data collection allow access to data collected outside of a clinical site. These data can give clinicians new insight into a patient’s everyday life. Digital phenotyping—the quantification of an individual’s phenotype through the use of data taken in situ—relies on machine learning models to potentially detect, diagnose, and treat a variety of different mental health disorders. Digital phenotyping thus has the potential to increase both the scalability and ecological validity of mental health treatment. Although digital phenotyping research is still in early stages, preliminary research shows promise for these data to help address the gap between mental health need and mental health care.
Introduction
Authors: Harter Thomas D. , Merlo Gia
Published: January 2025

The concept of medical professionalism is often talked about and treated as interchangeable with healthcare professionalism. However, it is noted here that medical professionalism is and should be considered distinct from healthcare professionalism, as healthcare professionalism is broadly inclusive of all the health professions, whereas medical professionalism is taken as applicable only to medical doctors. Reasons for this distinction include both the level of training necessary to be a medical doctor and the fiduciary bond between patients and physicians. This chapter then outlines the overall structure of the textbook, highlighting the importance of the narrative prologue and epilogues of each section and the uniqueness of the concluding chapter. In describing the structure, a brief description of each section and chapter is provided.
Faculty Development for Professionalism
Authors: Gillis Marin , Bolstad Judy
Published: January 2025

The faculty of medical trainees may feel it is an assault on their character to suggest that they may need formal training in medical professionalism prior to teaching it to students. However, training for medical professionalism requires developing skills just as much medical professionalism itself is a skill set. Yet, if medical professionalism education is to remain a self-regulated function of the profession, medical professionalism programs must develop curriculum for training not only the trainees but also the trainers. This chapter discusses a pathway forward for developing professionalism education among faculty as a means toward ensuring high-quality professionalism education for medical students.
Managing Spiritual Issues in Catholic-Affiliated Health Systems
Authors: Bedford Elliott Louis , Eberl Jason T.
Published: January 2025

This chapter highlights ways in which religiously affiliated health systems, specifically those of the Roman Catholic tradition, support and manage issues of spirituality in the provision of care, especially as they intersect issues of professionalism. Spirituality plays an explicit and distinguishing role in the mission, vision, and values of Catholic healthcare delivery. The chapter begins by drawing attention to the philosophy of medicine, founded in the Hippocratic tradition and revitalized by scholars such as Edmund Pellegrino, which animates the identity and mission of Catholic healthcare. Practical implications of this philosophy of medicine are illustrated in the context of end-of-life care. The final two sections elucidate the professional commitment to the spiritual dimension of healthcare and how healthcare professionals are formed within a Catholic healthcare institution. The chapter concludes by focusing on the specific practice of spiritual care, provided by both Catholic and non-Catholic professional chaplains, as a practical manifestation of the care of the whole person characteristic of the Catholic healthcare mission.
Well-Being
Authors: Carrese Joseph , Merlo Gia
Published: January 2025

Physician well-being is inextricably linked to medical professionalism . Historically, the stressful nature and circumstances of clinical work and operationalizing professionalism to require extreme levels of self-sacrifice, have together undermined physician well-being. This chapter explores the relationship between physician well-being and medical professionalism and argues that a modern and robust version of professionalism requires well-being to be a key element of professionalism as opposed to the historical experience that well-being is often a casualty of professionalism.
How Physicians Demonstrate and Maintain Professionalism Through Communication
Authors: Houchens Nathan
Published: January 2025

When patients and physicians engage in effective relationship-centered care, they each experience myriad important positive benefits. Patients note improved adherence with treatment plans, functional status, symptoms, quality of life, and rates of readmission and death. Physicians enjoy improved diagnostic accuracy and confidence and lower rates of burnout. Physicians personify professionalism with their patients through verbal (clear, concise, and inviting language; empathic statements) and nonverbal (bodily posture and positioning, gestures, eye contact) communication strategies. Scholarly literature on patient preferences for physician attire, a modifiable aspect of nonverbal communication that impacts the patient-physician relationship, is reviewed. Both physicians and patients may harbor biases and stereotype threat toward the other, which may lead to challenging situations involving harassment, discrimination, and microaggresions. In these moments, physicians can employ relationship-centered communication skills to proactively mitigate their own biases, repair relationship ruptures, and demonstrate support for themselves and other members of the healthcare team.